BIO 353 Cell Biology Class Organization PDF

instructor, TAs, and peers BIO 353 Class Organization BIO 353 Class Organization...

instructor, TAs, and peers BIO 353 Class Organization BIO 353 Class Organization BIO 353 Class Organization BIO 353 Instructor: The TAs Professor Shawn will serve Chen as the conduit for CellChen Instructor: Professor Shawn Biology communication between students and the TA: Rylee Close, instructor. Jenniferstudents Therefore, Melendez,should Reyna Gutierrez only use TA: Rylee Close, Jennifer Melendez, Reyna Gutierrez the Canvas Inbox tool to communicate with the Instructor TAs (CC’ingand TAsallLoading… have fouroffice hours of us), (see syllabus) rather than Instructor and TAs have office hours (see syllabus) sending emails to the instructor or individual TAs. Tips forThis approach success: ensures attend class, that clicker answer all course- questions, Tips for success: attend class, answer clicker questions, take notes,messages related complete are homework, studyinlecture centralized and one place, take notes, complete homework, study lecture and chapter allowingmaterials, communicate the instructor to beregularly consultedwithand the chapter materials, communicate regularly with the instructor, TAs, and provide clear andpeers consistent responses. instructor, TAs, and peers BIO 353 Class Organization BIO 353 Class Organization BIO 353 Class Organization BIO 353 Class Organization The TAs will serve as the conduit for Instructor: Professor Shawn Chen The TAs will serve as the conduit for communication between students and the communication between students and the Four closed-book instructor. exams,students Therefore, non comprehensive should only (100use pts TA: Rylee Close, instructor. Jenniferstudents Therefore, Melendez,should Reyna Gutierrez only use each) the Canvas Inbox tool to communicate with the the Canvas Inbox tool to communicate with the Active(CC’ing TAs allLoading… class participation four of us), rather than TAs (CC’ing Instructor and TAsallLoading… fouroffice have of us), rather hours than (see syllabus) Extra credits: sending emails to the instructor or individual sending emails to the instructor or individual Homework: Homework will be assigned to each lecture. You TAs. This approach ensures that all course- can earn extra credits toward the 400 total exam points if you TAs. Tips forThis approach success: ensures attend class, that clicker answer all course- questions, related submitmessages arebefore centralized in one place, your homework the deadline. One point for each related take notes,messages complete are centralized homework, studyinlecture one place, and allowing the instructor to be consulted and homework will be considered extra credit. (There are >20 lectures chapter allowingmaterials, communicate the instructor to beregularly consultedwithand the provide clear so >20 points extraand creditconsistent responses. can be added and possibly advance by a letter instructor, TAs, and provide clear andpeers consistent responses. grade if all homework is submitted on time). BIO 353 Class Organization BIO 353 Class Organization  get any point of class participation. Class participation and iClicker Alberts Bray Hopkin Johnson Lewis Raff Roberts Walter Alberts Bray Hopkin Johnson Lewis Raff Roberts Walter Active class participation is required, 10% of your overall grade. Class participation is monitored ONLY by your responses to clicker Essential Essential questions with an iClicker device during the class period. May participate in iClicker sessions using the iClicker Reef app on a Cell Biology smartphone or other mobile device or using a web browser on a computer. full participation points. Cell Biology Loading… Required to respond to iClicker questions in least 80% live lectures to earn FIFTH EDITION The 80% attendance requirement was chosenFIFTHtoEDITION provide flexibility and accommodate any University-sanctioned absences. Students should not contact instructors about any individual absences. Chapter 1 Chapter Long sanctioned absence: contact Office of1the Dean of Students Cells: The Fundamental Units of Life Fail to meetCells: The Fundamental the minimum Units requirement 80% iClicker participation of Life will not get any point of class participation. The Question to Answer The Question to Answer Alberts Bray Hopkin Johnson Lewis Raff Roberts Walter Cell Biology as a Discipline Essential The cell is the basic unit of all biology; all living organisms consist of one or more cells Cell Biology Our objective is to understand the structure and How doofyou FIFTH EDITION function cells,identify as found inan unknown animals, plants and How do you identify an unknown protein and study its function after microorganisms protein and study its function after Chapter 1 identification? Cells: identification? The Fundamental Units of Life The Question to Answer Cell Biology as a Discipline  Early studies of cells 1665 – Robert Hooke, using a microscope he constructed, observed a multitude of ‘tiny 1665 – Robert Hooke, using a microscope he compartments’ he called cellulae. constructed, observed a multitude of ‘tiny compartments’ he called cellulae. You don't need to memorize names or historical timelines. Focus on learning: 1) What is cell theory? 2) The four essential elements for success in science. Hooke’s microscope Hooke’s microscope Micrographia engraving of cork Micrographia engraving of cork “cells” “cells” Early studies of cells Early studies of cells Early studies of cells 1830’s – Improvements in magnification allowed 1830’s – Improvements in magnification allowed 1839 Robert– Theodor Brown toSchwann postulates observe what his a he called Robert Brown to observe what he called a unified nucleustheory of cells in plant cellular organization: he examined nucleus in plant cells he examined 1) All organisms consist of one or more cells 1838 –Matthias Schleiden postulated his theory 1838 –Matthias Schleiden postulated his theory Loading… 2) The cell is the basic unit of structure for all of cellular organization for plants: Loading… of cellular organization for plants: organisms 1) All plants consist of one or more cells 1) All plants consist of one or more cells 1855 – Karl Nageli extends Schwann’s theory 2) The cell is the basic unit of structure for all plants 2) The cell is the basic unit of structure for all plants by adding the third tenet of cell theory 3) All cells arise only from preexisting cells Early studies of cells  DNA, RNA and protein metabolism. Cell Theory Cell Biology weaves three disciplines together: Light Microscopy Cell theory is a Cytology: study of cellular structure and organization using Limit light of resolution microscope (1650 =onward) λ/2. (λ: and electron microscope (1935 cornerstone of cell biology wavelength in nanometer) onward). 1) All organisms consist of one or more cells Biochemistry For example, (1910 onward): study an instrument with of a cellular structure with 2) The cell is the basic unit non-microscopic methods and visible light wavelength studyofof cellular function by range of structure for all characterizing 400-700 nm, chemical the limitreactions of of biomolecules (enzyme- organisms catalyzed reactions, resolution metabolic pathways). is 200-350nm 3) Cells arise only by Molecular The bestbiology: study resolution of of how cellular functions are (1) light division from preexisting regulated and (2) microscopy is transmitted fromum. 200 nm or 0.2 one generation to another – cells by characterizing interactions between processes involving DNA, RNA and protein metabolism. Cell Biology weaves three disciplines together: Light Microscopy Light microscope let to the discovery of cells Cytology: study of cellular structure and organization using Limit light of resolution microscope (1650 =onward) λ/2. (λ: and electron microscope (1935 Cells are very diverse in size, shape, chemical wavelength in nanometer) onward). requirements, and function Biochemistry For example, (1910 onward): study an instrument with of a cellular structure with non-microscopic methods and visible light wavelength studyofof cellular function by range characterizing 400-700 nm, chemical the limitreactions of of biomolecules (enzyme- catalyzed reactions, resolution metabolic pathways). is 200-350nm Molecular The bestbiology: study resolution of of how cellular functions are (1) light regulated and (2) microscopy is transmitted fromum. 200 nm or 0.2 one generation to another – by characterizing interactions between processes involving DNA, RNA and protein metabolism. Light Microscopy TEM negative stain (Chen Lab) Electron Microscopy reveals the fine structure Electron Microscopy Electron Microscopy reveals the fine structure of a cell of a cell Mitochondria Electron microscopy – governed by Eukaryotes have different cell morphologies but Eukaryotes have wavelength different of electrons (thecell morphologies best resolution is 0.2 nm) but the same basic parts the same basic Transmission partsmicroscopy (TEM) electron Scanning electron microscopy (SEM) TEM negative stain (Chen Lab) Mitochondria The Endoplasmic Reticulum  Microscopy reveals typical cellular structures Why Study Cell Biology? Why Study Cell Biology? All cells are enclosed by a plasma membrane The cell is the basic structural and reproductive The cell is the basic structural and reproductive contain DNA as genetic information unit of all biology; all living organisms consist of unit of all biology; all living organisms consist of Eukaryotic cells Possess a nucleus (with chromosomes inside) and one or more cells. one or more cells. various membrane-bound organelles Cytoplasm: all of the cell content outside the nucleus Solve real world problems Solve real world problems Cytosol: cytoplasmic content outside membrane-enclosed organelles Examples: development of efficacious vaccines and Animal Examples: development of efficacious vaccines and and plant cells are typically 5-20 um. therapeutics: therapeutics: ZMAPP is originally developed at ASU! ZMAPP is originally developed at ASU! Cell Biology is fun! Cell Biology is fun! Rather than studying the three disciplines individually, Rather than studying the three disciplines individually, we will explore how these branches of science come we will explore how these branches of science come together to make life work! together to make life work! Summary Summary Cell theory Cell theory To understand: To understand: Why cell biology is important? Why cell biology is important? Homework: Canvas>Modules>Lecture 1 homework Homework: Canvas>Modules>Lecture 1 homework Before answering the homework questions, please review the following topics from BIO181: Before answering the homework questions, please review the following topics from BIO181: General cellular components General cellular components Their structure and function Their structure and function The central dogma The central dogma  Macromolecules structural organization Chemistry of the Cell Chemistry of the Cell Alberts Bray Hopkin Johnson Lewis Raff Roberts Walter Why Can't You Trust an Atom? All cell functions have a molecular and chemical basis All cell functions have a molecular and chemical basis Essential and are therefore described in terms of molecules and and are therefore described in terms of molecules and chemical reactions. Because they make up everything! chemical reactions. Cell Biology Predominant themes in the chemistry of the cell: of the cell: FIFTH EDITION Predominant themes in the chemistry Importance of carbon: backbone of biomolecules Loading… Importance of carbon: backbone of biomolecules Importance of water: solvent of living systems Importance of water:Lecture solvent of living 2 systems Importance of synthesis by polymerization of small Importance of synthesis by polymerization of small molecules: many biomolecules are polymers Chemical Components of Cells molecules: many biomolecules are polymers Importance of self-assembly: spontaneous formation of Macromolecules Importance of self-assembly: spontaneous formation of structural organization structural organization Chemistry of the Cell Why Can't You Trust an Atom? Atoms, Protons, Electrons All cell functions have a molecular and chemical basis and are therefore described in terms of molecules and Because they make up everything! chemical reactions. Predominant themes in the chemistry of the cell: Loading… Importance of carbon: backbone of biomolecules Importance of water: solvent of living systems Importance of synthesis by polymerization of small molecules: many biomolecules are polymers Protons are positively charged. Importance of self-assembly: spontaneous formation of Neutrons are electrically neutral. structural organization Electrons are negatively charged. Orbit around the nucleus in discrete “orbit” or shell. Why Can't You Trust an Atom?  Carbon= smallest element with the highest valency! Carbon = smallest element that can form the largest number of covalent bonds with other atoms Atoms, Protons, Electrons, Bonds Valency of atoms Covalent bond strength vs. atomic weight Valency is the number of electrons an element can share, lose or gain to attain stability. Loading… 1st, 2nd, and 3rd shell can hold maximally 2, 8,and 8 electrons, respectively. The strength of a covalent bond is inversely proportional to the atomic Atoms with outermost shell completely filled is stable and chemically unreactive. weights of the bonding elements. Atoms with outermost shell incompletely filled is unstable and chemically reactive. The smaller the atoms, the closer the nuclei and the electrons are to each other. Thus, a shorter and stronger covalent bond. React with other atoms to form molecules to achieve a completed outmost shell. By gaining or losing electrons to each other – forming an ionic bond. CompoundsCarbon= formedsmallest element by covalent with theof bonding highest valency!weight (small) atoms low atomic By sharing electrons – forming a covalent bond (strongest bond type) are more stable. Carbon = smallest element that can form the largest number of covalent bonds with other atoms Covalent bond strength vs. atomic weight Why? Why? and Why? Why carbon is the best candidate to form the backbone of biological macromolecules ? The strength of a covalent bond is inversely proportional to the atomic weights of the bonding elements. The smaller the atoms, the closer the nuclei and the electrons are to each other. Thus, a shorter and stronger covalent bond. Compounds formed by covalent bonding of low atomic weight (small) atoms are more stable.  Why? Why? and Why? Carbon Carbon Tetravalent: the smallest atom that can form the largest number (4) of covalent Tetravalent: the smallest atom that can form the largest number (4) of covalent bonds with other atoms. This allows it to form a diverse range of molecular Biological bonds macromolecules with other need atoms. This allows it totoform perform multiple a diverse and range of diverse molecular structures, which in turn can perform a wide variety of functions. functions. structures, Therefore, which they in turn can musta be perform wide variety of functions. Stable bonding: C is small and generally forms 4 covalent bonds with itself or Stable bonding: C isstable both structurally small and diverse forms 4 covalent bonds with itself or and generally with other small atoms such as O, H, N, and S. These diverse structures are stable with other small atoms such as O, H, N, and S. These diverse structures are stable enough to perform a wide set of functions. enough to perform a wide set of functions. Stereoisomers: When bonded to 4 different atoms or groups, tetrahedral carbon Stereoisomers: When bonded to 4 different atoms or groups, tetrahedral carbon gives rise to stereoisomers, adding another layer of diversity. gives rise to stereoisomers, adding another layer of diversity. Tetra-valency, stable associations with itself and other small atoms, and the ability Tetra-valency, stable associations with itself and other small atoms, and the ability to form tetrahedral stereoisomers—allow carbon to form a diverse array of stable, to form tetrahedral stereoisomers—allow carbon to form a diverse array of stable, carbon-containing molecules. This diversity and stability are crucial for carbon’s carbon-containing molecules. This diversity and stability are crucial for carbon’s role as the backbone of biomolecules, supporting the demanding functions required role as the backbone of biomolecules, supporting the demanding functions required of these molecules. of these molecules. Carbon Why? Why? and Why? Water Universal solvent in biological Tetravalent: the smallest atom that can form the largest number (4) of covalent systems – most life-sustaining bonds with other atoms. This allows it to form a diverse range of molecular reactions occur in an aqueous structures, which in turn can perform a wide variety of functions. environment. Stable bondingis: Cthe Why carbon is best smallcandidate and generally to forms form 4the covalent bondsof backbone with itself or biological Most abundant component of cells with other small atoms macromolecules Loading… ? such as O, H, N, and S. These diverse structures are stable enough to perform a wide set of functions. (75-85% by weight). Extracellular aqueous environment is Stereoisomers: When bonded to 4 different atoms or groups, tetrahedral carbon gives rise to stereoisomers, adding another layer of diversity. also vital for cells, allowing the Tetra-valency, stable associations with itself and other small atoms, and the ability exchange materials and energy with to form tetrahedral stereoisomers—allow carbon to form a diverse array of stable, their surroundings. carbon-containing molecules. This diversity and stability are crucial for carbon’s role as the backbone of biomolecules, supporting the demanding functions required of these molecules. Water has polarity! C is the smallest atom (strong bonds= stable) which has the highest valency (diversity) and can form stereoisomers (adding more diversity) Why? Why? and Why?  Water is special! Water Water Water is an Excellent Solvent Water can form up to 4 Water can form up to 4 hydrogen bonds with other hydrogen bonds with other (respective molecules. molecules.electronegativity) The polarity of water gives The polarity of water gives rise to unique properties: rise to unique properties: H-bonds lead to cohesion. H-bonds lead to cohesion. Temperature stabilizing Temperature stabilizing capacity (high heat capacity) – capacity (high heat capacity) – protect cells from temperature protect cells from temperature fluctuations. fluctuations. (respective electronegativity) Hydrophilic vs hydrophobic solutes Water Water is an Excellent Solvent Water can form up to 4 Water is an Excellent Solvent hydrogen bonds with other molecules. The polarity of water gives rise to unique properties: H-bonds lead to cohesion. Temperature stabilizing capacity (high heat capacity) – protect cells from temperature fluctuations. Hydrophilic vs hydrophobic solutes Water is an Excellent Solvent Polar water provides one of the driving forces of for forming  The hydrophobic effect is a unique organizing force, based on repulsion by the solvent (water) instead of attractive forces between hydrophobic molecules. For example, It is responsible for assembly of membranes of cells Polar water provides one of the driving forces of for forming Polar water provides one of the driving forces of for forming molecular Polar waterand cellularone provides structure: Hydrophobic of the driving Interaction forces of for forming molecular and cellular structure: Hydrophobic Interaction molecular and cellular structure: Hydrophobic Interaction The hydrophobic effect is a unique organizing force, based on repulsion by the solvent The hydrophobic effect is a unique organizing force, based on repulsion by the solvent (water) instead of attractive forces between hydrophobic molecules. For example, It is (water) instead of attractive forces between hydrophobic molecules. For example, it is The hydrophobic effect is a unique organizing force, based on repulsion by the solvent responsible for assembly of membranes of cells responsible for assembly of membranes of cells (water) instead of attractive forces between hydrophobic molecules. For example, it is responsible for assembly of membranes of cells Polar water provides one of the driving forces of for forming Synthesis by Polymerization molecular and cellular structure: Hydrophobic Interaction Some General Principles of Macromolecular Chemistry The biochemical basis of cell biology is understood through the function of macromolecules. 1. Each macromolecule is a polymer formed from small molecules (called monomers or subunits) linked together by covalent Most macromolecules are bonds (30 small molecule precursors: 20AA, 5 bases, 3 lipids, and 2 sugars). ordered arrays of linear polymers of small organic 2. Polymer chain is folded in one preferred conformation (unique shape) which is determined by the linear sequence of monomers molecules. The hydrophobic effect is a unique organizing force, based on repulsion by the solvent (water) instead of attractive forces between hydrophobic molecules. For example, it is responsible for assembly of membranes of cells Synthesis by Polymerization Some General Principles of Macromolecular Chemistry  Principle of Selfand Assembly Why? Why? and Why? Why? Why? Why? One structure requires one Principle of Self Assembly – the information required to specify specific mold to be the folding of macromolecules and their interactions to form cast. more complicated (3-D) structures with specific biological functions is inherent in the polymers themselves. No need for further information or energy input. Why biological macromolecules are made of polymers of subunits Mature Why macromolecules biological are held macromolecules together are made by noncovalent of polymers and of subunits instead of unique large molecules? instead of unique large covalent interactions.molecules? Chemical simplicity and efficiency: A limitless variety of polymers can be built from a small set of monomers One structure One structure requires one requires one The Chemistry of Life Is Special specific mold to be specific mold to be In That… cast. cast. It is based largely on carbon compounds. It depends most exclusively on chemical reactions that take place in aqueous solutions within a narrow range of temperatures. Chemical It utilizes simplicity and Macromolecules efficiency:molecules – - polymeric Chemical simplicity and efficiency: consisting of chains of chemical subunits linked end- to-end. A limitless variety of polymers can A limitless variety of polymers can beHomework: built from a small set of Canvas>Modules>Lecture 2 homework be built from a small set of monomers monomers The Chemistry of Life Is Special  Review Proteins are the most important and ubiquitous macromolecules Review Alberts Bray Hopkin Johnson Lewis Raff Roberts Walter in the cell Goals The of celllectures 3 and 4: and reproductive unit of Essential is the basic structural The cell is the basic structural and reproductive unit of all biology; all living organisms consist of one or more all biology; all living organisms consist of one or more cells Understand the principle of self assembly of proteins cells Cell Biology All cell functions have a molecular and chemical Howcell All basis, thefunctions shape andhave and therefore How protein structure of proteins a molecular are formed and chemical works are described in terms of basis, and therefore are described in terms of molecules and chemical reactions. molecules How protein Carbon containing How proteins Loading… andfunctions chemicalare reactions. controlled macromolecules are responsible are studied Carbon containing macromolecules are responsible for most of the structure and function in cells. Lecture for most of 3 and the structure 4 (Chapter and function in cells.4) synthesized by polymerization of small molecules (require energy!) Protein synthesized Structureof and by polymerization Function small molecules (require self-assembly: spontaneous formation of structural energy!) organization self-assembly: spontaneous formation of structural organization Review Proteins are the most important and ubiquitous macromolecules in the cell Proteins are polymers of amino acids Goals The of celllectures 3 and is the basic 4: and reproductive unit of structural all biology; all living organisms consist of one or more Understand the principle of self assembly of proteins cells 20 standard amino acids Howcell All thefunctions shape andhave structure of proteins a molecular are formed and chemical How protein basis, works are described in terms of and therefore Structure: molecules How protein How proteins Carbon Loading… andfunctions chemicalare are studied containing reactions. controlled macromolecules are responsible central carbon amino group for most of the structure and function in cells. synthesized by polymerization of small molecules (require carboxyl group (acid) energy!) R group (side chain) self-assembly: spontaneous formation of structural variable group organization confers unique chemical properties of the amino acid Proteins are the most important and ubiquitous macromolecules in the cell  group of second amino acid directionality Amino Acids are Linked by Polypeptide Polypeptide Each polypeptide chain consists of a backbone that supports the Backbone Peptide Covalent Each polypeptide chain consists of a backbone that supports the different amino acid side chains Backbone different amino acid side chains Bonds Backbone is made up of the core atoms of amino acids (N-C-C) Backbone isHmade up of the core atoms of amino acids (N-C-C) Projecting from the repetitive N-C-C backbone are side chains H Projecting H N C C O - + from the repetitive N-C-C backbone are side chains Side chains give each amino acid its unique properties Side H chains give eachOamino acid its unique properties R Loading… Covalent peptide bond forms peptide when carbon atom of the bond carboxyl group of one amino Peptide “grow” in one direction: N acid shares electrons with the to C nitrogen atom from the amino Polypeptide chain has an intrinsic group of second amino acid directionality Polypeptide Types of Side Chains Types of Side Chains Each polypeptide chain consists of a backbone that supports the Backbone Amino Acids with non-polar side chains different amino acid side chains Backbone is made up of the core atoms of amino acids (N-C-C) Projecting from the repetitive N-C-C backbone are side chains Side chains give each amino acid its unique properties Hydrophobic side chains They tend to localize in the interior of the folded 3-D protein structure in aqueous environment Size and flexibility matter! Types of Side Chains Amino Acids with non-polar side chains  Size and flexibility matter! side chain. Cysteine: the only AA can form covalent (disulfide) bond with its side chain Size and charge matters! Amino Acids with Polar or Charged Side Chains Amino acid Side Chains Polypeptide is a polymer formed from amino acids linked together by covalent peptide bonds Polypeptide chain is folded in one preferred conformation You don’t have to remember the structure of each (unique shape) which is determined by the linear sequence of amino amino acid for this course. acids But if you are given the name of an amino acid, you NEED to know whether this amino acid has a non- Loading… polar, polar, negatively charged, or positively charged side chain. You also NEED to know Cysteine is the only amino acid that can form covalent (disulfide) bond with its Hydrophilic side chains side chain. cluster on the surface of the folded 3-D structure in aqueous environment Cysteine: the only AA can form covalent (disulfide) bond with its side chain Size and charge matters! Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Polypeptide is a polymer formed from amino acids linked Amino acid Side Chains Polypeptide is a polymer formed from amino acids linked Protein Folding utilizes weak Noncovalent together by covalent peptide bonds Polypeptide chain is folded in one preferred conformation together by covalent peptide bonds bonds to stabilize its structure (unique shape) which is determined by the linear sequence of Polypeptide chain is folded in one preferred conformation You don’t have to remember the structure of each (unique shape) which is determined by the linear sequence of Polypeptide amino acids chains are very flexible due to free rotation amino amino acid for this course. acids of the bonds in the backbone Folding is not random – it is guided by the side chains, But if you are given the name of an amino acid, you that is, it is determined by the amino acid sequence NEED to know whether this amino acid has a non- Loading… Specifically, folding is guided by the balance of side chain. Loading… polar, polar, negatively charged, or positively charged tendencies for forming many weaker noncovalent bonds There are four types of noncovalent bonds. Can you You also NEED to know Cysteine is the only amino name them? acid that can form covalent (disulfide) bond with its side chain. Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company Polypeptide is a polymer formed from amino acids linked Protein Folding utilizes weak Noncovalent together by covalent peptide bonds bonds to stabilize its structure  Ionic Bonds Hydrogen Bonds Hydrogen Bonds Strong electrostatic van der Waals attractions attractive forces between a Weak force produced by fluctuations Hydrogenin bonds formclouds electron when charged R- group in one Hydrogen bonds form when of atoms that are brought inaclose hydrogen atom is proximity part of a polypeptide chain a hydrogen atom is “sandwiched” between two and an oppositely charged “sandwiched” between two Individually very weak, but strongest between side electron-attracting atoms, R- group in another part of electron-attracting atoms, chains containing carbon and hydrogen atoms only usually oxygen or nitrogen the chain usually oxygen or nitrogen Hydrogen bonds can form Hydrogen bonds can form between two side chains, between two side chains, between two parts of the between two parts of the peptide backbone or peptide backbone or between the backbone and between the backbone and a side chain. a side chain. Hydrogen Bonds van der Waals attractions van der Waals attractions Hydrophobic interaction Weak force produced by fluctuations in electron clouds Weak force produced by fluctuations Hydrogenin bonds formclouds when Nonpolar side chains containing carbon and hydrogen atoms are electron of atoms that are brought in close proximity shielded from water because of unfavorable energetic interactions. of atoms that are brought inaclose hydrogen atom is proximity Individually In very weak, order to be shielded buthidden they are strongest in the between side protein interior. “sandwiched” between two Individually very weak, but strongest between side electron-attracting atoms, chains containing carbon and hydrogen atoms only Hydrophobic forces help proteins fold into compact conformations chains containing carbon and hydrogen atoms only usually oxygen or nitrogen Hydrogen bonds can form between two side chains, between two parts of the peptide backbone or between the backbone and a side chain. van der Waals attractions Hydrophobic interaction  and hydrophobic forces Protein folding uses all four Disulfide Bonds – covalent! Disulfide types of Bonds – covalent! Disulfide bonds help reinforce a favored protein Non- Disulfide bonds help reinforce a favored protein conformation conformation covalent bonds (ionic bonds) and hydrophobic forces Disulfide Bonds – covalent! Levels Disulfide of help bonds Protein Structure reinforce a favored protein Tertiary Structure conformation Primary – amino acid sequence Tertiary Structure Long distance Secondary – Local folding patterns, alpha helix and beta sheets “Whole molecule folding” Depends almost entirely on interactions Tertiary – 3D folding of a polypeptide chain between the various R-groups (side chains), regardless of where they are in Quaternary – Association of 2 or more polypeptides to form a the primary sequence, driven by the multimeric protein tendency to form: H-bonds ionic bonds van der Waals attractions hydrophobic interactions anchored by disulfide bond bridges The variation of aa and their relative position will affect these interaction profoundly Levels of Protein Structure  difference! Protein Domains Protein structure & function Protein structure & function Domains are discrete regions of Sickle cell anemia folded structure frequently associated with specific functions Function depends on structure any segment Function of a on structure depends polypeptide chain that can It all begins with the It allindependently fold begins with the into a order of amino acids order compact,of amino stableacids (Tertiary) what determines that order of structure what determines that order of amino acids? amino acids? consists of Domain usually 100-250 amino acids The amino acid sequence is determined by DNA The amino acid sequence is determined by DNA A slight change in amino acid sequence can impact Modular unit from which A slight many change larger inproteins amino acid sequence can impact are protein’s structure and function protein’s structure and function constructed Even a single amino acid change can make all the Even a single Different amino acid domains in a change Example: can makebacterial all the regulatory protein difference! CAP; one large domain binds cAMP difference! protein are associated with and one small domain binds DNA different functions Sickle cell anemia Sickle cell anemia Primary Structure of Cytochrome-C Loading… To avoid such risks, Chen’s group turned to a protein subunit or domain…. The Question to Answer Primary Structure of Cytochrome-C  these hydrogen bonds The Question to Answer Common Folding Patterns in protein secondary structure Common Folding Patterns in protein secondary structure Helix Conformation of each protein is unique Conformation of each protein is unique However, two folding patterns are often present in 2o However, two folding patterns are often present in 2o structure (local folding of polypeptide chain by structure (local folding of polypeptide chain by interaction of adjacent amino acid) How do you identify an unknown interaction of adjacent amino acid) helix protein and helix study its function after sheet sheet identification? Folding patterns are common because they result from Folding patterns are common because they result from hydrogen bonds that form between N-H and C=O hydrogen bonds that form between N-H and C=O groups using repetitive elements of the polypeptide groups using repetitive elements of the polypeptide backbone backbone Amino acid side chains are NOT involved in forming Amino acid side chains are NOT involved in forming these hydrogen bonds these hydrogen bonds Common Folding Patterns in protein secondary structure Helix Helix Conformation of each protein is unique Sheet However, two folding patterns are often present in 2o structure (local folding of polypeptide chain by interaction of adjacent amino acid) helix sheet Folding patterns are common because they result from hydrogen bonds that form between N-H and C=O groups using repetitive elements of the polypeptide backbone Amino acid side chains are NOT involved in forming these hydrogen bonds Helix Sheet  CAP; one large domain binds cAMP protein are associated with and one small domain binds DNA different functions The Question to Answer The Question to Answer Quaternary Structure Quaternary Structure is related to subunit Loading… How doand interactions you identify an unknown How do you identify an unknown applies only to protein multimeric and study its function after To avoid such risks, proteins protein and study its functionChen’s after group turned to a protein subunit identification? (those containing identification? or domain…. multiple polypeptides) The Question to Answer Quaternary Structure Quaternary Structure Levels of Protein Structure Quaternary Structure Quaternary Structure is related to subunit is related to subunit interactions and How doand interactions you identify an unknown applies only to applies only to multimeric proteins protein multimeric and study its function after proteins (those containing identification? (those containing multiple polypeptides) multiple polypeptides) Full 3-dimensional helices and structure formed by the Protein molecule AA sequence Sheets formed as a complex of peptide bond entire polypeptide. Backbone more than one Side chains H-bond polypeptide chain. H-bond, ionic bond, von Side chains der Waals, hydrophobic Same as tertiary interactions, disulfide structure bond Quaternary Structure Levels How the of Protein shape Structure and structure of proteins are  Once folded proteins are stabilized by the same bonds: H-, ionic, von der Waals, Question: How do proteins function? hydrophobic and disulfide bond How the shape and structure of proteins are Protein Functions Biological Functions of Proteins Depend on Their Protein Functions formed Ability to Bind Other Molecules Selectively Principle of Self Assembly - The information required to specify the folding of proteins and their interactions to form complex structures with specific biological functions is inherent in the Proteins are the most important and ubiquitous Any substance that is bound by a polypeptide themselves, determined by the chemistry of the amino acids and their sequential order in Proteins are the most important and ubiquitous the polypeptides macromolecules protein is referred toin asthe cell a ligand macromolecules Folding in the is driven by the tendency of cell Nine major classes forming disulfide and noncovalent bonds Enzymes region of –the catalysts proteinin biochemical reactions Nine major classes The which between different AA elements associates with a ligand is called Enzymes – catalysts in biochemical reactions Structural proteins – provide shape and support The unique chemical nature of side chains abinding site Structural proteins – provide shape and support Motility – contractile or flagellating proteins (charge, size, hydrophobicity) and the Motility position – contractile of each side or flagellating chain will determine if proteins Regulatory proteins – coordinate cellular activities Binding sites can involve many Regulatory and where these bondsproteins can form – coordinate cellular activities Transport proteins – substances into or out of cells separate parts of the polypeptide Transport Various proteins tendencies and – substances into or out of cells forces either Hormonal proteins – signals between distant cells chain that are brought together by cooperate or oppose one other until Hormonal proteins – signals reachingbetween distant cells Receptor protein proteins folding – or (tertiary response to chemical stimuli a balance: a fully folded protein with the Defensive proteins – protect against disease Receptor proteins – response to chemical stimuli quaternary structures) lowest free energy. Defensive proteins – protect against disease Storage proteins – storage of amino acids Once folded proteins are stabilized by the The ability of a protein molecule to Storage same bonds: proteins H-, ionic, – storage von der Waals, of amino acids Question: How do proteins function? bind to just one or a few molecules Question: How do proteins function? hydrophobic and disulfide bond out of many thousands = specificity Biological Functions of Proteins Depend on Their Specificity of ligand binding is determined by Ability to Bind Other Molecules Selectively the geometry of individual noncovalent bonds Any substance that is bound by a Effective binding only occurs when the surface contours of the ligand protein is referred to as a ligand fit very closely to the protein Effective binding also requires many bonds to be formed The region of the protein which simultaneously associates with a ligand is called a binding site Poor matching surfaces result in few noncovalent bonds, and the two molecules dissociate rapidly- preventing unwanted associations Binding sites can involve many between mismatching molecules. separate parts of the polypeptide chain that are brought together by protein folding (tertiary or quaternary structures) The ability of a protein molecule to bind to just one or a few molecules out of many thousands = specificity Specificity of ligand binding is determined by  Relevant COVID-19 Example Relevant Antibodies COVID-19 are highly specific Example Relevant COVID-19 Example Specific binding of the Spike (S) protein (RBD domain) Certain antibodies that bind to specific domains of the S of SARS-CoV-2 Certain and antibodies human that ACE2 bind to