Protein Structure and Function: Study Notes

Protein Structure and Function

Introduction

Proteins are essential macromolecules in all living organisms, responsible for a wide range of biological functions. Their structure is intricately related to their function, and understanding this relationship is fundamental in biology.

Biological Roles of Proteins

Functions of Proteins in Cells

• Sensing light: Proteins such as opsins in the eye detect and respond to light stimuli.

• Defending cells against viruses: Antibodies and other immune proteins recognize and neutralize pathogens.

• Breaking down food polymers: Enzymes catalyze the hydrolysis of complex molecules into simpler ones for absorption.

• Changing cell shape: Structural proteins like actin and tubulin are involved in cell movement and maintaining cell shape.

• Summary: All of the above processes directly involve proteins.

The Flow of Genetic Information

Central Dogma of Molecular Biology

• DNA is transcribed into messenger RNA (mRNA).

• mRNA is translated into protein.

• Proteins determine the physical traits of organisms by performing structural, enzymatic, and regulatory roles.

Proteins as Polymers

Monomers of Proteins

• Proteins are polymers of amino acids.

• Each protein is a chain of amino acids linked by peptide bonds.

Amino Acids: Structure and Properties

General Structure of Amino Acids

• Each amino acid contains:

  • An amino group ($-NH_2$)

  • A carboxyl group ($-COOH$)

  • A side chain (R group) that varies among amino acids

  • A central carbon atom (alpha carbon)

  • A hydrogen atom

• Key functional groups present on every amino acid: an amino group and a carboxyl group.

Diagram: (See image for structure; central carbon bonded to amino group, carboxyl group, hydrogen, and R group.)

Classification of Amino Acids by R Group

• Nonpolar amino acids: R group contains only hydrogen and carbon atoms. These are hydrophobic and do not form hydrogen bonds.

• Polar amino acids: R group contains electronegative atoms (e.g., oxygen, nitrogen) and can form hydrogen bonds.

• Charged amino acids: R group is either acidic (negatively charged) or basic (positively charged) at physiological pH.

• Example: If a newly discovered amino acid has an R group with only hydrogen and carbon, it is nonpolar.

Peptide Bond Formation

Condensation and Hydrolysis Reactions

• Condensation reaction: Joins two amino acids by forming a peptide bond and releasing water.

• Hydrolysis reaction: Breaks a peptide bond by adding water, releasing individual amino acids.

Equation for condensation:

$\text{Amino acid}_1 + \text{Amino acid}_2 \rightarrow \text{Dipeptide} + H_2O$

Equation for hydrolysis:

$\text{Dipeptide} + H_2O \rightarrow \text{Amino acid}_1 + \text{Amino acid}_2$

Levels of Protein Structure

Primary Structure

• The primary structure is the unique sequence of amino acids in a polypeptide chain.

• Sequence is written from the amino (N-) terminus to the carboxyl (C-) terminus.

Secondary Structure

• Formed by hydrogen bonds between backbone atoms (not side chains).

• Common types:

  • Alpha (α) helix

  • Beta (β) pleated sheet

Tertiary Structure

• Overall 3D shape of a single polypeptide chain.

• Stabilized by interactions between side chains, including:

  • Hydrogen bonds

  • Ionic bonds

  • Hydrophobic interactions

  • Disulfide bonds (covalent bonds between cysteine residues)

  • Van der Waals forces

Quaternary Structure

• Association of two or more polypeptide chains (subunits) into a functional protein complex.

• Examples: Hemoglobin (tetramer), DNA-binding proteins (dimers).

Summary Table: Levels of Protein Structure

Level	Description	Stabilizing Interactions
Primary	Sequence of amino acids	Peptide bonds
Secondary	Local folding (α-helix, β-sheet)	Hydrogen bonds (backbone)
Tertiary	3D shape of polypeptide	Hydrogen bonds, ionic bonds, hydrophobic interactions, disulfide bonds, van der Waals
Quaternary	3D shape of polypeptide	Same as tertiary (between subunits)

Protein Folding and Function

Denaturation and Renaturation

• Disrupting hydrogen bonds (e.g., by heat or chemicals) can denature proteins, causing loss of secondary, tertiary, and quaternary structure, but primary structure remains intact.

• Some proteins can refold (renature) and regain function if the denaturing agent is removed.

Protein Structure Determines Function

• Proper folding is essential for protein activity.

• Example: Calmodulin is inactive when disordered, but becomes active and functional upon binding calcium ions and folding into a specific shape.

Enzymes and Specificity

Active Site and Catalysis

• Most enzymes are highly specific, catalyzing only one type of chemical reaction.

• Specificity is determined by the geometry and types of amino acids in the active site of the enzyme.

Effects of Amino Acid Changes

Mutations and Protein Function

• Changing a single amino acid (point mutation) can alter the primary structure, and may affect tertiary structure and function.

• Example: Sickle cell anemia is caused by a single amino acid substitution in hemoglobin, leading to altered protein function and disease.

Summary Table: Amino Acid Properties

Type	R Group Characteristics	Example Amino Acids
Nonpolar	Hydrocarbon side chains	Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Phenylalanine, Tryptophan, Proline
Polar	Side chains with O or N; can form H-bonds	Serine, Threonine, Tyrosine, Asparagine, Glutamine
Acidic	Negatively charged at pH 7	Aspartate, Glutamate
Basic	Positively charged at pH 7	Lysine, Arginine, Histidine

Key Takeaways

• Proteins are polymers of amino acids, whose sequence determines their structure and function.

• Protein structure is organized into four levels: primary, secondary, tertiary, and quaternary.

• Proper folding is essential for protein function; even a single amino acid change can have significant effects.

• Enzyme specificity is determined by the structure of the active site.