Lecture 4 Protein PDF

Proteins Macromolecules lectures (Proteins, Carbohydrates & Nucleic acids) Learning Outcomes. Describe the relationship between atoms and molecules. Be able to describe the different types of bonds that occurs between atoms and molecules. Describe the molecules of life. Proteins, carbohydrates an...

Proteins Macromolecules lectures (Proteins, Carbohydrates & Nucleic acids) Learning Outcomes. Describe the relationship between atoms and molecules. Be able to describe the different types of bonds that occurs between atoms and molecules. Describe the molecules of life. Proteins, carbohydrates and nucleic acids. Define the terms carbohydrate, protein and nucleic acid. Be able to draw representative carbohydrate, proteins and nucleic acid structures Be able to describe their main functions in biological systems Briefly outline how they are synthesised and broken down. Be aware that ALL life are made up of four classes of macromolecules. Matter: Any type of physical material. Composed of; 1. Elements. 2. Molecules. 3. Compounds. 1. Elements. Atoms of a single type, in pure form. Atoms are the fundamental units of matter. 2. Molecules Two or more atoms held together by a chemical bond. H2, N2, O2, H2O. These may be atoms of the same element (H2) or of different elements H plus O (a compound) 3. Compound A molecule of two or more different elements. A compound has characteristics very different from it’s component elements. CH4, H2O, CO2. All compounds are molecules but not all molecules are compounds. Diagram for illustration Carbon atom purposes Bonding of atoms (intermolecular forces-between atoms) Covalent bond (co = shared) When two atoms share electrons Example: H2 2 Hydrogen atoms share their electron to form H2 molecule. Diagrams for illustration purposes Sharing of electrons between atoms in a molecule can be equal or unequal. 1. Non-polar covalent bonds Equal ‘pull’ on shared electrons by both atoms. E.g. H2 and a peptide bond in proteins, disulphide bond in proteins. 2. Polar covalent bonds Unequal ‘pull’ on shared electrons by one atom. E.g. H20 Ionic Bonds (No Sharing! Non Covalent!) Complete transfer of electron from one atom to another. No sharing so not covalent = non-covalent bond Example: NaCl Cation: Na gives up electron Na+ Anion: Cl takes electron Cl- (Attractions between oppositely charged ions) https://www.youtube.com/watch?v=QXT4OVM4vXI Non-covalent bonds A non-covalent bond is a type of chemical bond that typically bond between macromolecules. They do not involve sharing a pair of electrons. Two important types for biology. 1. Hydrogen bonds ( between molecules) 2. A hydrogen bond occurs when a hydrogen atom covalently bonded to an electronegative atom is attracted to another electronegative atom. Attraction between partial positive charge on hydrogen of a molecule with partial negative charge on an atom in another molecule E.g. Water. Diagrams for i l l u s t ra t i o n Van der Waals interactions Attraction between transient (temporary) regions of positive charge in one molecule with a transient negative charge in another molecule. (transient dipole). (Important for the stability of fatty acid interactions in phospholipid membranes) Proteins, carbohydrates, nucleic acids and lipids are called macromolecules. All except lipids are polymers composed of long chains of small molecules called monomers. Polymers: Molecular structures built from a large number of similar units bonded together. Lipids are macromolecules but NOT polymers (not composed of long chains of monomers). Synthesis and breakdown of macromolecules requires protein/enzyme catalysts. https://www.youtube.com/watch?v=7e2IkQHxszM Functions of proteins 1. Enzymes are proteins that facilitate biochemical reactions, for example, pepsin is a digestive enzyme in your stomach that helps to break down proteins in food. 2. Antibodies are proteins produced by the immune system to help remove foreign substances and fight infections. 3. DNA-associated proteins regulate chromosome structure. Example histones. 4. Contractile proteins are involved in muscle contraction and movement, Example, actin and myosin 5. Structural proteins provide support in our bodies, for example, the proteins in our connective tissues, such as collagen and elastin. 6. Hormone proteins which co-ordinate bodily functions, for example, insulin controls our blood sugar concentration by regulating the uptake of glucose into cells. 7. Transport proteins move molecules around our bodies, for example, haemoglobin transports oxygen through the blood. Enzymatic proteins Defensive proteins Function: Selective acceleration of Function: Protection against disease chemical reactions Example: Antibodies inactivate and help Example: Digestive enzymes catalyze the destroy viruses and bacteria. hydrolysis of bonds in food molecules. Antibodies Enzyme Virus Bacterium Storage proteins Transport proteins Function: Storage of amino acids Function: Transport of substances Examples: Casein, the protein of milk, is Examples: Hemoglobin, the iron-containing the major source of amino acids for baby protein of vertebrate blood, transports mammals. Plants have storage proteins in oxygen from the lungs to other parts of the their seeds. Ovalbumin is the protein of body. Other proteins transport molecules egg white, used as an amino acid source across membranes, as shown here. for the developing embryo. Transport protein Ovalbumin Amino acids for embryo Cell membrane Hormonal proteins Receptor proteins Function: Coordination of an organism’s Function: Response of cell to chemical activities stimuli Example: Insulin, a hormone secreted by Example: G-protein mediates intracellular the pancreas, causes other tissues to take signaling pathways. up glucose, thus regulating blood sugar concentration. Receptor protein High Insulin Normal Signaling blood sugar secreted blood sugar molecules Contractile and motor proteins Structural proteins Function: Movement Function: Support Examples: Motor proteins are responsible Examples: Keratin is the protein of hair, for the undulations of cilia and flagella. horns, feathers, and other skin appendages. Actin and myosin proteins are responsible Insects and spiders use silk fibers to make for the contraction of muscles. their cocoons and webs, respectively. Collagen and elastin proteins provide a fibrous framework in animal connective Actin Myosin tissues. Collagen Muscle 30 µm tissue Connective 60 µm tissue Animation: Contractile Proteins © 2017 Pearson Education, Inc. Animation: Defensive Proteins © 2017 Pearson Education, Inc. Animation: Enzymes © 2017 Pearson Education, Inc. Animation: Hormonal Proteins © 2017 Pearson Education, Inc. Animation: Receptor Proteins © 2017 Pearson Education, Inc. Animation: Sensory Proteins © 2017 Pearson Education, Inc. Animation: Storage Proteins © 2017 Pearson Education, Inc. Animation: Structural Proteins © 2017 Pearson Education, Inc. Animation: Transport Proteins © 2017 Pearson Education, Inc. The molecules of life: macromolecules 1. Proteins:. The units that build proteins are called amino acids Proteins are macromolecules composed of monomers called amino acids. https://www.youtube.com/watch?v=zm-3kovWpNQ Ted Talk 2013. Protein changing shape. Composition of PROTEINS (polypeptides): Proteins are polymers. Long chains made of repeating units of amino acids. Illustration Amino acids have two important functional groups (a functional group means a group of atoms in a molecule that have characteristic chemical reactions regardless of the rest of the molecule): These are: carboxylic acid group -COOH amine group -NH2 Be able to draw the generalised amino a c i d → An Amino group (NH2) A Carboxyl group (acid, COOH) A variable R Group A central carbon. There are 20 different amino acids that may occur in the proteins of all living cells. The 20 amino acids are the molecular ‘toolbox’ for making proteins https://www.youtube.com/watch?v=qBRFIMcxZNM Characteristics of the amino acid R groups. The R group (side chain) determine the unique characteristics of an amino acid. There are 20 different R groups. The R groups can be: Nonpolar covalent bonding with electrons shared equally between the atoms. No charge. (hydrophobic R group) Polar covalent (uneven sharing of electrons, hydrophilic R group) One atom has a slightly negative charge. The other atom has a slightly positive charge. Ionic bonds: Charged hydrophilic ions. Complete transfer of electron from one atom to another. (Negatively charged side group is acidic, Positively charged side group is basic). Formation of proteins (polypeptides) Amino acid are connected to each other by condensation/dehydration reactions. The reaction removes a hydroxyl group (OH) from the carboxyl end of one amino acid and a hydrogen from the amino group (NH2) of another amino acid. A covalent peptide bond is formed and a molecule of water is released. Diagram for illustration purposes Repeating this process yields a long chain of amino acids forming a polypeptide. Polypeptides have directionality - from the N–terminus to the C-terminus. An incoming amino acid must be added at the C-terminus. Hydrolysis reactions to break polypeptide chains needs an input of a molecule of water per peptide bond. Animation: Protein Structure Introduction Protein structure/conformation and function A functional protein is composed of one or more polypeptides that must fold correctly. Diseases due to inappropriate protein folding. E.g.: Alzheimer's & Parkinson's diseases. A protein’s function depends on its specific conformation (3D shape/structure). Four hierarchical levels of structural organisation for proteins; 1. Primary structure. The amino acids and their linear sequence in a protein. Understand the Diagram (no need to draw). Know that the code for protein synthesis Occurs in the DNA. DNA—mR NA — Protein Primary structure determines protein function. A single amino acid that is in the wrong position can cause a vital protein to malfunction. Sickle Cell Disease Here the amino acid valine is inserted instead of glutamic acid at position 6. This leads to a dysfunctional protein and the condition of sickle cell anaemia. Diagram Illustration only Know which amino acid substitution accounts for sickle cell disease 2. Secondary structure The patterns of hydrogen bonds (non covalent) formed along the polypeptide chain. These bonding interactions that occurs at regular intervals along the chain of amino acids stabilise the polypeptide. Two variations of secondary structure can occur from this Hydrogen bond interaction; (i) Alpha helix (ii) Beta pleated sheets Alpha helix formation In the α helix, the CO group of residue n forms a hydrogen bond with the NH group of residue n+ 4 A hydrogen bond occurs when a hydrogen atom covalently bonded to an electronegative atom is attracted to another electronegative atom. A part of an antibody molecule has surface loops (shown in red) that mediate interactions with other molecules Diagram to illustrate H bond interactions that contribute to the stability of the secondary structure.  Individually, these H bond interactions are weak, but collectively are very strong. The strong structural properties of silk is due to beta pleated sheets The presence of so many hydrogen bonds makes each silk fibre stronger than steel or kevlar. 3. Tertiary structure (3-D structure of the molecule) Further folding occurs due to more bond interactions involving the R groups. Areas with Alpha helices and Beta sheets fold again to form tertiary structure. Tertiary structure stabilisation due to the following bonds; 1. Hydrogen bonds between atoms of the polar R groups (Non covalent) 2.Ionic interactions between positively and negatively charged R groups. (Non covalent) (attractions or repulsions Some amino acids have charged R groups, which attract oppositely charged R groups and repel those with like charges). 3. Hydrophobic interactions among hydrophobic (non polar amino acid R groups). (Non covalent) 4.Disulphide bonds (Two sulfur containing amino acids R groups forming a disulfide bond - a covalent bond - the strongest bond involved in tertiary structure stabilisation). 5. Van der Waals interaction: Weak interactions of non polar amino acid R groups (Non covalent) Properties and functions of amino acid side chains dictate how a protein will fold (final structure)  Hydrogen bonds, Ionic interactions and hydrophobic interactions are weak bonds  Disulfide bonds are strong bonds Diagrams for illustration The final of a protein is known as its native conformation structure which is biologically active Proteins composed of just one polypeptide the tertiary structure is the final active form of the protein Summary of bond interactions in the Tertiary structure Diagram for illustration. You will not be asked to draw it. Animation: Tertiary Protein Structure Animation: Quaternary Protein Structure  Heme Iron β subunit α subunit α subunit β subunit Hemoglobin 4. Quaternary structure Quaternary structure results from more than one chain of amino acids (polypeptide) interacting to make a protein. Bonds interactions are the same as tertiary structures. Quaternary arrangements result in either Globular or Fibrous proteins. Globular proteins are folded such that the polar, or hydrophilic, amino acids are arranged on the outside and the nonpolar, or hydrophobic, amino acids on the inside of the three-dimensional shape. This arrangement is responsible for the solubility of globular proteins in water. E.g. Haemoglobin, Insulin Fibrous proteins: These have special mechanical properties which result from their unique structure. Fibrous proteins are insoluble and have important structural functions in cells. E.g. Collagen (connective tissue), Elastin (blood vessels), Keratin (hair) https://www.youtube.com/watch?v=qBRFIMcxZNM Animation summary protein structure Mutations in gene for collagen protein can lead to a number of diseases  Denaturation: A protein’s conformation can change in response to the physical and chemical conditions. Alterations in pH, salt concentration, temperature, or other factors can unravel or denature a protein. These forces disrupt the hydrogen bonds, ionic bonds, and disulfide bridges that maintain the protein’s shape. Some proteins can return to their functional shape after denaturation (ribonuclease), so the process can be reversed, but others cannot, especially in the crowded environment of the cell. Diagrams for illustration