Protein Structure and Function: Study Notes for General Biology

Key Biological Molecules: Proteins

Introduction to Proteins

Proteins are the most abundant and versatile macromolecules in living organisms. They perform a wide variety of functions, including catalyzing biochemical reactions, providing structural support, and regulating cellular processes.

• Composed of: 20 different amino acids with unique side chains

• Polymerization: Amino acids are linked by peptide bonds to form polypeptides

• Protein Structure: Organized into four levels: primary, secondary, tertiary, and quaternary

• Protein Function: Diverse roles in living cells, such as enzymes, structural proteins, transporters, and signaling molecules

Protein Composition and Amino Acid Structure

Atomic Composition

• Elements: Carbon (C), Hydrogen (H), Oxygen (O), Nitrogen (N), and sometimes Sulfur (S)

Amino Acid Core Structure

• Each amino acid consists of a central (alpha) carbon atom bonded to:

  1. Amino group (-NH2)

  2. Carboxyl group (-COOH)

  3. Hydrogen atom (H)

  4. Unique side chain (R group)

• The R group determines the chemical properties and identity of each amino acid.

Peptide Bond Formation

Linking Amino Acids

• Amino acids are joined by peptide bonds, which are covalent bonds formed between the carboxyl group of one amino acid and the amino group of another.

• This reaction releases a molecule of water (dehydration synthesis).

Equation for Peptide Bond Formation:

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

Levels of Protein Structure

Primary Structure

The primary structure of a protein is its unique sequence of amino acids, held together by peptide bonds. This sequence determines all higher levels of structure and ultimately the protein's function.

• Polypeptide chain: Linear sequence from N-terminus (amino end) to C-terminus (carboxyl end)

• Sequence diversity: With 20 amino acids, even a short chain (e.g., 10 residues) can have $20^{10}$ possible sequences (10,000,000,000 combinations)

Secondary Structure

Secondary structure refers to local folding patterns within a polypeptide, stabilized by hydrogen bonds between backbone atoms (not side chains).

• Alpha helix (α-helix): Right-handed coil stabilized by hydrogen bonds

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

• Stabilization: Hydrogen bonds between the carbonyl oxygen and amide hydrogen of the backbone

Tertiary Structure

The tertiary structure is the overall three-dimensional shape of a single polypeptide chain, resulting from interactions among side chains (R groups).

• Functional conformation: Required for protein activity (e.g., enzyme function, binding DNA, forming channels)

• Stabilizing interactions:

  • Hydrogen bonds

  • Hydrophobic interactions

  • Van der Waals forces

  • Ionic bonds

  • Disulfide bridges (covalent bonds between cysteine residues)

Quaternary Structure

Some proteins consist of more than one polypeptide chain (subunit). The quaternary structure describes the arrangement and interaction of these subunits.

• Examples: Hemoglobin (tetramer), some enzymes (dimers, trimers, etc.)

• Function: Subunit interactions are essential for the protein's biological activity

Determinants of Protein Structure and Function

Role of Amino Acid Sequence

• The sequence of amino acids (primary structure) determines the protein's final 3D shape and function.

• Example: Sickle cell anemia is caused by a single amino acid substitution (Glu to Val) in hemoglobin, leading to abnormal protein aggregation and distorted red blood cells.

Importance of 3D Shape

• Proper folding is essential for protein function.

• Denaturation (unfolding) by heat or chemicals disrupts structure and function, but some proteins can refold if conditions are restored.

• Experiment: Ribonuclease can refold and regain function after denaturation if disulfide bonds are reformed.

Molecular Chaperones

• Proteins called molecular chaperones assist in the proper folding of other proteins.

• Chaperones prevent aggregation and help achieve the correct conformation, which is necessary for function.

Summary Table: Levels of Protein Structure

Level	Description	Stabilizing Bonds/Interactions	Example
Primary	Linear sequence of amino acids	Peptide bonds	Insulin polypeptide chain
Secondary	Local folding into α-helices and β-sheets	Hydrogen bonds (backbone)	α-helix in keratin
Tertiary	Overall 3D shape of a polypeptide	Hydrogen bonds, ionic bonds, hydrophobic interactions, disulfide bridges	Myoglobin
Quaternary	Association of multiple polypeptides	Same as tertiary (between subunits)	Hemoglobin (tetramer)

Key Terms

• Amino acid: Building block of proteins, containing an amino group, carboxyl group, hydrogen atom, and R group

• Peptide bond: Covalent bond linking amino acids in a protein

• Denaturation: Loss of protein structure and function due to unfolding

• Molecular chaperone: Protein that assists in the folding of other proteins

• Quaternary structure: Arrangement of multiple polypeptide subunits in a protein complex