Introduction to Cell Biology & Biochemistry

Protein Structure

Overview of Protein Structure

  • Graphic representation of protein structure.

  • Different structural forms of proteins:

    • Tertiary structure

    • Fibrous and globular proteins

    • Quaternary structure

Graphic Representation of Protein Structure

Ribbon Model

  • Presents the peptide backbone as a ribbon, effectively conveying the rigid planar nature of the peptide bond.

  • Reveals secondary structure elements such as helices and sheets.

  • Note: Side chains of amino acids are not shown in this representation.

  • The ribbon’s arrow indicates chain direction (N to C direction) for β-strands.

Alternative Representations

  • Options include showing all amino acids or displaying specific groups of amino acids.

Model Illusions

  • Be cautious of misrepresentations in models:

    • The ball & stick model can create an illusion that the α-helix has a hollow center, which is inaccurate.

    • A model that uses real Van der Waals radii removes this misleading appearance.

Protein Tertiary Structure

Definition

  • The overall three-dimensional shape of a protein, derived primarily from a single polypeptide chain.

  • Tertiary structure is influenced by different secondary structures present.

Types of Proteins

Fibrous and Globular Proteins

  • Proteins are classified into two main categories:

Fibrous Proteins

  • Described as chains that form long strands or sheets.

  • Typically consist of a single type of secondary structure (e.g., α-helices or β-sheets).

  • Function: Provide structural support, shape, and protection.

  • Examples:

    • Keratin

    • Collagen

    • Silk fibroin

Globular Proteins

  • Characterized by chains that are folded into spherical or globular shapes.

  • Often contain multiple secondary structures.

  • Functions include being enzymes and regulatory proteins.

Examples of Fibrous Proteins

  • Keratin:

    • Insoluble in water and has a high hydrophobic amino acid content both internally and externally.

  • Closely packed chains cause surface residues to be buried.

  • Collagen:

    • Details of the unique amino acid sequence:

    • Comprised of repeating sequences of Gly-X-Pro or Gly-X-Hyp.

    • Glycine residues (shown in red) are oriented inward, allowing for tight packing (non-hollow structure).

    • Unique Helical Secondary Structure:

      • Left-handed helix with a turn completion of 3 amino acids per turn, as opposed to the common right-handed helix (a helix typically follows 3.6 amino acids per turn).

      • The arrangement comprises a triple helical structure where three chains are supertwisted about each other.

  • Silk Fibroin:

    • Composed mainly of alanine (Ala) and glycine (Gly).

    • Exhibits a secondary structure predominantly of β-conformation with fully extended chains.

    • Structure features layered antiparallel β-sheets stabilized by hydrogen bonding and hydrophobic interactions.

    • Interlocking R groups (colored yellow for Gly and purple for Ala) prevent longitudinal sliding of the stacked β-sheets.

Collagen Fibrils

  • Crosslinks between lysine and hydroxylysine in the triple helices contribute to a more rigid structure.

  • Superhelical twisting increases tensile strength, surpassing that of steel wire of equivalent diameter.

Globular Proteins

Structural Characteristics

  • Defined by polypeptide chains folded back on themselves extensively, creating a compact structure.

  • Provides a diverse range of structures suited for various functions:

    • Includes enzymes, transport proteins, motor proteins, regulatory proteins, immunoglobulins, and more.

Dimensions and Characteristics

  • Sizes and compositions include:

    • 13,700 Da, 124 AA, 26% α-helical, 35% β-sheets with 4 S-S bonds.

    • 14,600 Da, 129 AA, 40% α-helical, 12% β-sheets with turns and loops, 4 S-S bonds.

    • 12,400 Da, 104 AA, 40% α-helical with turns, irregular coils, and extended segments.

Example of a Globular Protein: Myoglobin

Structural Features

  • Composed of a single polypeptide chain of 153 amino acids.

  • Contains one iron porphyrin (heme) group.

  • Structure features:

    • 8 α-helices (accounting for >70% of amino acids) along with some bends.

    • Functionality: Primarily involved in muscle oxygen storage, particularly in the muscles of diving mammals (whales, seals, and dolphins).

  • Most of the spatial structure is occupied by amino acid side chains, with hydrophobic residues located within the protein's interior.

Heme Group

  • Defined as a prosthetic group commonly found in various proteins, including myoglobin and hemoglobin.

  • Formed by an iron ion at the center of the heterocyclic organic compound known as porphyrin.

  • Critical for binding, transporting, or storing oxygen.

Protein Quaternary Structure

Definition

  • Some proteins consist of two or more separate polypeptide chains (subunits), which can be identical or different.

  • The arrangement of these subunits forms the three-dimensional complexes that define the quaternary structure.

Characteristics of Multisubunit Proteins

  • Proteins containing multiple polypeptide chains are generally termed multimeric proteins.

  • This structure enables small molecule interactions, which can influence protein-protein binding and lead to significant changes in protein activity.

  • Subunits are held together by:

    • Weak bonds (hydrogen bonds, ion bridges, Van der Waals interactions).

    • Covalent bonds (disulfide bridges).

    • A combination of both types of bonds.

Immunoglobulins

  • Example of quaternary structure seen in antibodies with antigen-binding sites.

Hemoglobin Structure

Features

  • Consists of 64,000 Da total weight, with 4 polypeptide chains (making it a tetramer).

  • Contains 4 heme groups, one associated with each polypeptide chain.

  • The protein part, referred to as globin, consists of 2 alpha (α) chains and 2 beta (β) chains.