Protein Structure

Introduction to Protein Structure

Proteins are essential macromolecules in biological systems, performing a wide array of functional and structural roles.

Peptide Linkage and the Peptide Bond

Objectives

1. Understand function and types: Identify roles proteins play in biological systems.

2. Describe the peptide bond: Define properties, formation, and hydrolysis.

3. Identify 4 levels of structure: Differentiate between primary, secondary, tertiary, and quaternary structures.

4. Interpret features: Relate characteristics to stability and function.

5. Conformational stability: Understand the relationship between stability, denaturation, and function.

Functions of Proteins

• Catalysis: Enzymatic activity in chemical reactions.

• Transport: Carrying substances across membranes or within organisms.

• Contractile mechanisms: Involved in muscle contraction and movement.

• Protection: Role in immune response and defense.

• Hormonal regulation: Acting as hormones to regulate body functions.

• Structural support: Frameworks for cells and tissues.

Types of Proteins

• Simple Proteins: Made only of amino acids.

• Conjugated Proteins: Contain non-polypeptide components (e.g., heme in hemoglobin).

• Membrane Proteins: Interact with biological membranes.

• Globular Proteins: Spherical and often water-soluble (e.g., enzymes).

• Fibrous Proteins: Elongated and usually structural (e.g., collagen).

Levels of Protein Structure

Primary Structure

• Linear sequence of amino acids (e.g., Ala, Asp, Lys). It determines function and folding.

Secondary Structure

• $\alpha$-Helix: Main chain wrapped helically; alpha-carbons spaced $1.5 \text{ \AA}$ apart. Hydrogen bonds form every $4^{\text{th}}$ amino acid.

• $\beta$-Sheet: Parallel/anti-parallel strands stabilized by hydrogen bonding; residues alternate above/below the sheet.

• $\beta$-Turn: Connects anti-parallel strands via hydrogen bonds between the $1^{\text{st}}$ and $4^{\text{th}}$ residues.

Tertiary Structure

• 3D arrangement of all atoms, including side-chain interactions.

• Stabilization: Non-covalent (H-bonds, salt bridges, hydrophobic) and covalent (disulfide bonds between cysteines).

Quaternary Structure

• Arrangement of multiple polypeptide chains (subunits).

• Includes complex globular proteins (hemoglobin) and fibrous proteins (collagen).

Denaturation

• Loss of higher-order structure (secondary, tertiary, quaternary) leading to a loss of function.

• Proteins can often refold if the original conditions are restored.

Collagen

• Major structural protein, accounting for $25\%$ of total human protein.

• Type I: Most abundant form, consisting of two $\alpha 1$ chains and one $\alpha 2$ chain.

• Structure: Sequence repeats of $\text{Gly-X-Y}$. Forms a left-handed helix stabilized by hydroxyproline.

• Vitamin C: Essential for hydroxyproline formation and triple helix stability.

Defects in Collagen Synthesis

• Scurvy: Vitamin C deficiency leading to connective tissue decay.

• Osteogenesis Imperfecta: Brittle bones resulting from glycine substitution in the collagen chain.

Summary

• Protein function is fundamentally dictated by its structure.

• Peptide bonds are rigid, polar, and non-ionizable.

• Structural hierarchy flows from Primary $\rightarrow$ Secondary $\rightarrow$ Tertiary $\rightarrow$ Quaternary.

• Overall stability relies on a combination of covalent and non-covalent bonds.