Protein Structure and Function

Overview

Proteins are essential macromolecules that perform a vast array of functions in living organisms. Their structure, determined by the sequence and properties of amino acids, is critical to their function. Understanding protein structure and function is fundamental in general biology.

Proteins: Diversity and Function

General Properties of Proteins

• Abundance: Proteins account for more than 50% of the dry weight of most cells.

• Cellular Quantity: A typical liver cell contains approximately protein molecules.

• Diversity: The human body can produce between 50,000 to 1 million different proteins.

• Functional Range: Proteins are responsible for nearly every function in an organism due to their structural diversity.

• Largest Known Protein: Titin (also called connectin) is the longest known protein, with 34,350 amino acid residues in its canonical form.

Major Types of Proteins and Their Functions

Amino Acids: The Building Blocks of Proteins

General Structure of Amino Acids

• Monomers of Proteins: Amino acids are the building blocks (monomers) of proteins.

• Core Structure: All amino acids share a common structure: a central (alpha) carbon atom bonded to an amino group (), a carboxyl group (), a hydrogen atom, and a variable side chain (R group).

• R Group: The R group (side chain) is what makes each amino acid unique and determines its properties.

General formula:

Classification of Amino Acids by Side Chain Properties

• Electrically Charged Side Chains: Can be acidic (negatively charged) or basic (positively charged), forming ionic and hydrogen bonds.

• Polar Side Chains: Have partial charges, allowing formation of hydrogen bonds.

• Nonpolar Side Chains: Lack charged or electronegative atoms, do not form hydrogen bonds, and are hydrophobic.

Protein Structure: Levels of Organization

Primary Structure

• Definition: The unique sequence of amino acids in a polypeptide chain, determined by the gene encoding the protein.

• Peptide Bonds: Amino acids are joined by peptide bonds, forming a polypeptide backbone.

• Importance: The primary structure dictates all higher levels of protein structure and ultimately the protein's function.

Secondary Structure

• Definition: Local folding of the polypeptide chain into structures stabilized by hydrogen bonds between backbone atoms.

• Main Types:

  • Alpha helix (α-helix): A coiled structure stabilized by hydrogen bonds.

  • Beta pleated sheet (β-sheet): Sheet-like structure formed by hydrogen bonds between parallel or antiparallel strands.

Tertiary Structure

• Definition: The overall three-dimensional shape of a polypeptide, resulting from interactions among R groups (side chains).

• Stabilizing Interactions: Includes hydrogen bonds, ionic bonds, hydrophobic interactions, and disulfide bridges.

• Function: Determines the protein's specific function by creating a unique active site or binding surface.

Quaternary Structure

• Definition: The association of two or more polypeptide chains (subunits) to form a functional protein complex.

• Examples: Hemoglobin (four subunits), collagen (three subunits).

• Not all proteins have quaternary structure; only those with multiple polypeptide chains.

Protein Folding and Function

Importance of Correct Folding

• Folding: Proteins must fold into their correct three-dimensional shape to function properly.

• Assistance: Molecular chaperones often help proteins fold correctly.

• Misfolding: Incorrectly folded proteins can lead to diseases such as Alzheimer's, Parkinson's, ALS, and prion diseases (e.g., Bovine Spongiform Encephalopathy).

Effects of Amino Acid Changes and Bond Disruption

• Single Amino Acid Changes: Even one amino acid substitution can disrupt protein structure and function (e.g., sickle cell anemia).

• Bond Disruption: Disruption of hydrogen bonds, ionic bonds, or disulfide bridges can denature proteins, causing loss of function.

Summary Table: Levels of Protein Structure

Example: Hemoglobin

• Hemoglobin is a quaternary protein composed of four polypeptide subunits, each with its own heme group for oxygen binding.

• Mutation in the primary structure (e.g., sickle cell mutation) can alter the protein's shape and function.