Proteins

Proteins

Functions of Proteins

  • Gene Coding

    • Humans have approximately 20,000 genes, each coding for a core protein.

  • mRNA and Protein Variation

    • Gene copies can be alternatively spliced, potentially leading to over 100,000 different proteins.

Variation in Proteins

  • Sources of Variation

    • Number of amino acids (20 standard, >20 modified).

    • Sequence of amino acid chains.

    • Alternative splicing and post-translation modifications.

The Study of Proteins - Proteomics

  • Proteomics Defined

    • The field dedicated to studying the vast diversity and functions of proteins.

  • The Proteome

    • The complete set of proteins in an organism.

  • Structure-Function Relationship

    • Protein function is determined by its structure, which is dictated by the amino acid sequence.

  • Impact of Mutations

    • Gene mutations can alter amino acid sequences, affecting protein structure and function.

Protein Structure

  • Levels of Organization

    • Biochemists categorize protein structure into several levels.

  • Mass Measurement

    • Protein masses are often expressed in daltons (e.g., 64 kDa).

Primary Structure

  • Definition

    • The sequence of amino acids in a polypeptide chain, linked by peptide bonds.

  • Terminology

    • Each amino acid is referred to as a "residue" or "moiety."

Secondary Structure

  • Definition

    • The local spatial arrangement of the polypeptide backbone, excluding side chains.

  • Hydrogen Bonding

    • Hydrogen bonds form between NH and C=O groups of amino acids.

Forms of Secondary Structure

  • Main Types

    • Alpha helix and beta (β) sheet.

The Alpha Helix

  • Structure

    • Right-handed coil with 3.6 amino acids per turn and a vertical distance of 5.4 Å per turn.

Functional Properties of Alpha Helices

  • Presence in Proteins

    • Common in many proteins; keratin is primarily composed of alpha helices.

  • Coiled Coil Structures

    • Two alpha helices wound together, stabilized by weak interactions and disulfide bridges.

Alpha Helices and Collagen

  • Collagen Characteristics

    • Most abundant protein in humans, fibrous, and forms a triple helix.

    • Haemoglobin is made ‘entirely’ out of alpha helices

Stability of Alpha Helices

  • Factors Affecting Stability

    • Electrostatic interactions, bulkiness of R groups, interactions between R groups, and proline residues.

The Beta (Pleated) Sheet

  • Structure

    • Composed of beta strands held together by hydrogen bonds.

Stability of Beta Sheets

  • Types

    • Parallel and anti-parallel beta sheets, with anti-parallel being more stable.

Importance of Beta Sheets

  • Trans-Membrane Proteins

    • Proteins like porins, which facilitate molecular movement across cellular membranes.

Tertiary Structure

  • Definition

    • Further folding of the polypeptide chain determined by side-chain interactions. Side chains can be hydrophillic, hydrophobic, charged etc. Proteins exist in aqueous environment so hydrophobic side chains will force folding into 3D structure, pointing side chains away from the water.

      Tertiary structures contain common combinations of secondary nature. Most proteins cointain combinations of very common supersecondary structures such as:

Forces in Tertiary Structure

  • Stabilizing Forces

    • Disulfide bonds, electrostatic interactions, and other forces contribute to stability.

Quaternary Structure

  • Definition

    • Composed of multiple polypeptides, often greater than 100 kDa, forming a functional protein.

Stabilization of Quaternary Structure

  • Types of Bonds

    • Similar to tertiary structure, stabilized by hydrogen bonds,