Biology I: Protein Structure and Function

• BG143 is a Biology I course that covers Protein Structure and Function.

Introduction to Protein Structure and Function

• Cells produce tens of thousands of unique proteins.
• Amino acids, discovered in Stanley Miller's experiment and found in meteorites, are the building blocks of proteins.
• Amino acids were likely abundant during chemical evolution.

The Origin of Life

• A protein must possess information, evolution, and replication to have been the initial spark of life.

The Structure of Amino Acids

• Most proteins are made from just 20 amino acids.
• Amino acids are composed of a central carbon atom bonded to a hydrogen atom (H), an amino functional group (NH2), a carboxyl functional group (COOH), and a variable "side chain" (R group).

Amino Acids in Water – pH 7

• Amino and carboxyl groups ionize in water.
• The amino group acts as a base and attracts a proton, becoming NH3+.
• The carboxyl group acts as an acid and donates a proton, becoming COO-.
• Ionization helps amino acids stay in solution and makes them more reactive.

The Nature of Side Chains

• The 20 amino acids differ only in the unique R-group, or side chain, attached to the central carbon.
• R-groups differ in their size, shape, reactivity, and interactions with water.
• Amino acids with hydroxyl, amino, carboxyl, or sulfhydryl functional groups in their side chains are more chemically reactive than those with side chains composed of only carbon and hydrogen atoms.
• R-groups can be grouped into three types: charged (acidic (-) and basic (+)), uncharged polar, and nonpolar.

Charged R-groups

• Charged R-groups are hydrophilic and readily dissolve in water.
• They can form ionic interactions with oppositely charged side chains.

Polar R-groups

• Polar R-groups are hydrophilic and readily dissolve in water.
• Polar R-groups can form hydrogen bonds.

Nonpolar R-groups

• Nonpolar R-groups are hydrophobic..
• Instead of dissolving, they coalesce in water and do not form hydrogen bonds.

20 Major Acids

• Amino acids are ranked according to how likely they are to interact with water.
• From highest to lowest, these are isoleucine, valine, leucine, phenylalanine, methionine, alanine, glycine, cysteine, tryptophan, tyrosine, proline, threonine, serine, histidine, glutamate, asparagine, glutamine, aspartate, lysine and arginine

Learning Objectives - Amino Acids

• Learning objectives include describing the basic structure of an amino acid.
• Also describing explaining why and how the side chains affect the structure and function of each amino acid.

How do Amino Acids Link to form Proteins?

• Proteins are macromolecules made of smaller subunits.
• Subunits are monomers ("one-part"), and monomers link together (polymerize) to form polymers ("many-parts").
• Amino acids are the monomers that make up proteins.

Polymerization of Proteins in Early Earth

• Monomers polymerize through condensation (dehydration) reactions, which involve the loss of a water molecule.
• Hydrolysis is the reverse reaction and breaks polymers apart by adding a water molecule.
• Polymerization requires energy and is nonspontaneous, monomers would not self-assemble into a polymer and decreases the entropy of the molecules.
• During chemical evolution, polymerization would occur only if the amino acid concentration was very high.
• Polymers on a mineral surface are protected from hydrolysis, so polymerization may have been able to occur.

The Peptide Bond: A Condensation Reaction

• Amino acids polymerize when condensation reactions bond the carboxyl group of one amino acid to the amino group of another; this is called a peptide bond (C-N bond).
• The peptide bond is unusually stable because a pair of valence electrons on nitrogen are partially shared in the C-N bond.

Some Peptide Terminology

• Directionality.
  • End starts with the amino group referred to as N-terminus
  • End starts with carboxyl group referred to as C-terminus
• Written N-terminus on the left by convention.
• A chain of fewer than 50 amino acids is an oligopeptide (“few-peptides") or a peptide.
• A chain of more than 50 amino acids is a polypeptide ("many-peptides"). _ Proteins are the complete, functional form of the molecule.

Amino Chains are Flexible

• Peptide forms the backbone
• Single bonds on either side of the peptide bond can rotate
• R-group Orientation extended our
• Side chains can interact with each other or water.

Learning Objective - Synthesis

• Includes an understanding the synthesis of a peptide chain, including formation of the peptide bond through dehydration synthesis

Protein Structures are Incredibly Diverse

• Diverse sizes and shapes lead to diverse chemical properties!

What Do Proteins Look Like?

• All proteins have four basic structures: primary, secondary, tertiary, and quaternary.

Primary Structure

• The unique sequence of amino acids is the protein's main feature.
• The number of primary structures is practically limitless.
  • 20 types of amino acids are available.
  • Lengths range from two amino acids to tens of thousands.

Changes to Primary Structure Affect Protein Function

• The amino acid R-groups affect a polypeptide's properties and function.
• A single amino acid change can radically alter protein function.

Secondary Structure

• It is formed by hydrogen bonds between carbonyl groups and amino groups.
• Can occur only when a polypeptide bends so that C=O and N-H groups are close together.
• Types of secondary structure include α-helices and ß-pleated sheets.
• Depends on the primary structure. Also, some amino acids are more likely to be involved in a-helices; others in ẞ-pleated sheets. _ Increases stability by way of the large number of hydrogen bonds

Secondary Structure Example

• Example is Spider Silk Proteins.
• Spiders produce several types of silk; one type is dragline silk.
• Dragline silk is six times stronger than a steel fibre of the same diameter.
• Strength is due to Beta-pleated sheets in proteins' structures.
• The total amount of backbone-to-backbone hydrogen bonds results in high-strength material.
• Biotechnology is used to mass-produce spider-silk proteins for use as surgical sutures and bulletproof vests.

Tertiary Structure

• Results from interactions between R-groups or between R-groups and the peptide backbone.
• Causes the backbone to bend and fold, contributes to the distinct 3D shape of the polypeptide.

Tertiary Structure: Important R-group interactions

• Important R-group interactions are hydrogen bonds, Ionic bonds, Hydrophobic interactions, Van der Waals interactions, Covalent disulfide bonds

Quaternary Structure

• It is formed by the bonding of two or more polypeptide subunits.
• Stabilized by interactions between R-groups or peptide backbones.
• The quaternary structure is based on tertiary structure, which is based on secondary structure, which is based on primary structure.

Normal Structure is Crucial Function

• A changing primary sequence can alter quaternary shape and hence the function of protein.

Normal Folding is Crucial to Function

• Protein folding often occurs spontaneously because of hydrogen bonds and van der Waals interactions.
• A denatured (unfolded) protein is unable to function normally.
• In cells, molecular chaperones help proteins fold correctly.

Protein Shape is Flexible

• Each protein has a characteristic folded shape that is necessary for its function.
• Many proteins have a disordered shape when they are inactive.
• Folds into ordered, active conformation when the active protein is needed.
• Control of where or when to fold is how some proteins are regulated.

Misfolding Can Be “Infectious"

• Prion diseases involve improperly folded forms of normal proteins.
• The amino acid sequence does not differ from a normal protein; rather shape is radically different.
• Affects other normal prion structure, that leads to degeneration of the brain tissue
• Creutzfeldt-Jakob disease is the most prion illness found in humans

Protein Functions are as Diverse as Protein Structures

• Proteins provide: Catalysis, Defence, Movement, Signalling, Structure, and Transport

Enzymes as Catalysts

• Catalysis may be the most important protein function.
• An enzyme is a protein that functions as a catalyst.
• Substrates are the reactants in enzyme-catalyzed reactions.
• The active site is the location on an enzyme where substrates bind.

Enzymes as Catalysts - Reactions

• Reactions take place when reactants collide in precise orientation.
  • And they have enough kinetic energy to overcome repulsion between the electrons that come in contact during bond formation.
• As catalyst
  • Brings substrates together in precise orientation so that electrons involved in the reaction can interact
  • Decreases the amount of kinetic energy reactants need to have for the reaction to proceed

Activation Energy and Rates of Chemical Reactions

• Activation energy (Ea) of a reaction is the amount of free energy needed to reach the intermediate condition, or transition state.
• Reactions occur when reactants have enough kinetic energy to reach the transition state.
  • The kinetic energy of molecules is a function of their temperature.
• Reaction rates depend on
  • The kinetic energy of reactants
  • The activation energy of the reaction (the free energy of the transition state)

Catalysts and Free Energy

• Catalyst: a substance that lowers a reaction's activation energy.
• Catalysts decrease the free energy of the transition state.
• They do not change ΔG and are not consumed in the reaction.
• Enzymes are protein catalysts and typically catalyze only one reaction.

How Enzymes Work

• Enzymes are able to catalyze reactions so specifically because they bring substrates together in precise orientations.
• Substrates bind to the enzyme's active site.
• An induced fit is undergone by many enzymes when substrates bind to the active site.
• Enzymes stabilize the transition state and lower the activation energy required for the reaction to proceed through interactions.

How do Enzymes Work?

• Reactant bind to an active site.
• "Induced fit" results in tighter binding of the substrate to the active site.

The Steps of Enzyme Catalysis

• Three steps of Enzyme Catalyst
  • Initiation
  • Transition state facilitation
  • Termination

Do Enzymes act alone?

• Some enzymes require cofactors to function normally.
• These are either metal ions or small organic molecules called coenzymes.
• These act at a location other than the active site

Enzyme Regulation

• Most Enzymes are affected by molecules that are not part of the enzyme itself
• Competitive inhibition occurs
  • When a molecule similar in size and shape to the substrate competes with the substrate for use of the active site
• Allosteric regulation -Occurs when a mole causes a change in enzyme shape by binding to the enzyme a location other than the active site
  • Regulators can can activate or deactivate the enzyme

What Limits the Rate of Catalysis?

• Enzymes are saturable
• Speed increases linearly at low substrate concentrations.
• Increase slows as substrate concentration increases.
• Reaction rate reaches max at high substrate concentrations.
• Eventually all enzymes show this type of saturation kinetics.
• At certain times active sites can't accept any faster.

Physical affects on Enzyme Function

• Enzymes are at their best at certain temp and pH
  • Temp affects the movement of the substrates and enzyme
  • pH affects the enzyme's shape and activity

Learning Objectives - Enzymes

• Describe the four levels of protein structure.
• Explain the relationship between protein folding and function.
• Provide examples of why proteins are essential to cell function.
• Explain what an enzyme is and why enzymes are needed to help chemical reactions proceed in living cells

Was the First Living Entity a Protein??

• Several observation argue self replicating is more than a protein:
  1. Amino acids were abundant in the prebiotic soup.
  2. Proteins are the most efficient catalysts known.
  3. A self-replicating molecule had to act as a catalyst for the assembly and polymerization of its copy.
• First self replicator probably needed to have a sold or model

The General Structure Of A Nucleotide

• Structures are built out of nucleic bonds.
• Nucleotides are composed of phosphate groups.
• Ribonucleotides are monomers of RNA.
  • Ribose is found in sugar
  • Has a -OH group bonded to 2' carbon
• Deoxyribonucleotides are monomers of DNA
  • Deoxyribose that means lacking oxygen -H instead of carbon

Types of Nitrogenous Bases

• Purines:
  • Adenine (A)
  • Guanine (G)
• Pyrimidines:
  • Cytosine (C)
  • Uracil (U): only in ribonucleotides
  • Thymine (T): :only in deoxyribonucleotides

ATP is an Example of a Nucleotide

• The amount of phosphate groups raises the potential energy of the monomer.

Could Chemical Evolution Produce Nucleotides?

• Simulations have not produced nutleotides.
• Sugars and purines.
• Pyrimidines are not easily sythesis
• Need ribose to form.

Nucleotides Polymerize to Form Nucleic Acids

• Polymerization of nucleic acids
• A condensation is made
  • bond between the carbon of one substrate and the -Oh carbon of another - Forming a sugar -phosphate backbone

DNA and RNA Strands Are Directional

• Each end has 5 phosphate
• Sequence is writtern in 5 →3
• This sequence comprises the prime structure.

The Polymerization of Nucleic Acids is Endergonic

• Comes from catalyzed processes. The transfer of one or more phosphate groups to substrate molecule
• This raises the potential and enabled edergonic

Learning Objectives - Nucleic Acids

• Identify the three main, basic components of a nucleotides
• Formation of nucleic acids that are attached to the sugar Explain now how DNA and RNA is different

DNA’S Secondary Structure

• Scientist new that the shape of DNA was due to the backbone
• It always had a base that way equal in numbers _ Used crystallography to get measurement

Secondary Structure: DNA Strands for Antiparallel Helix

• Watson and Crick determined
  • Strands had hydrogen bonds
  • They determine a structure
  • Hydrophobic sugar out
  • Nitrogen base in

Determining Complimenary Base

• Purine fits into the double helix
• Hydrogen bonds form between G-C and A-T

DNA Strands Form an Antiparallel Double Helix

• Hydrophobic interactions cause DNA to twist
• One twist every 10 base pairs.
• Negatively charged phosphate groups face out, making DNA hydrophilic overall
• Major and minor grooves

DNA Functions as an Information Molecule

• DNA stores and transmits bio info
• Contains the base for language for living

DNA Replication

• Complementary base pairing provides a simple mechanism for DNA replication.
  • Each strand can serve as a template for the formation of a new complementary strand.
  • Contains information required for a copy of itself to be made.
  • More on this in Week 9...

The DNA Double Helix Is A Very Stable Structure

• DNA is a reabile way to store info and resistant chemical damages
  • DNA has never been has never been observe

How Does RNA Structurally Differ From DNA?

• sugar -phosphate. Contains ribose instead of deoxyribose.

RNA's Secondary Structure

• Forms with complemenary base pairing
• Bases form hydrogen bonds
• RNA folds and forms hairpin structure

Tertiary Structure of RNA molecules

• Forms more complex shapes and diverse range reactivates.

Compare and Contrast DNA and RAN

• DNA is a double stranded helix and stores genetic information.
• RNA is single stranded and plays role is gene expresssion

Features of RNA

• More reactive than DNA. _ Can act as an enzyme
• Capable of self replication.

THE FIRST LIFE-FORM: RNA

• Template of copy,
• Ribozyme catalyze could be isolated

Information processing replication , evolution to the process

This lesson covers protein structure and function in Biology I. It discusses the origin of life, amino acids, and their behavior in water. The lesson also touches on how cells produce a variety of proteins.