Protein Morphology: Globular vs. Fibrous

Protein Morphology Overview

• Defines overall appearance based on final folded form.

• Two main groups: globular and fibrous.

• Approximately $90\%$ of proteins are globular.

• Fibrous proteins, though fewer types, can constitute over $1/3$ of total protein content in some organisms due to high synthesis amounts.

Globular Proteins

• Shape: Globe or spherical.

• Solubility: Water-soluble.

• Structure: Composed of typical secondary structures ($\alpha$-helices, $\beta$-sheets, or both).

• Composition: Hydrophobic core with hydrophilic, solvent-exposed portions.

• Stability: Marginally stable due to weak non-covalent interactions.

• Dynamics: Dynamic, allowing structural changes for function.

• Functions: Varied, including enzymes, receptors, binding proteins.

• Example: Actin – globular, rich in $\alpha$-helices, few $\beta$-sheets, achieving a spherical shape.

Fibrous Proteins

• Role: Important for structural support.

• Stability: High level, crucial for their structural function.

• Unique Properties: Distinct amino acid composition, residue modifications, specific non-covalent and covalent interactions contributing to stability.

Keratin

• Location: Key structural protein in skin, hair, and nails.

• Amino Acid Composition: High amounts of Cys residues.

• Stability: Disulfide bonds formed from Cys sulfhydryl groups provide strength.

• Structures:

  • $\alpha$-keratin: Helical, structurally distinct from standard $\alpha$-helix.

  • $\beta$-keratin: Sheet-like structure, distinct from standard $\beta$-sheet, formed by extending $\alpha$-keratin.

• Higher-Order Structure: Coiled coil structures form extended fibrils, which further interact to create complex structures (e.g., cuticle, fingernails).

Collagen

• Location: Connective tissue (tendons, cartilage, bone matrix, cornea, blood vessels, skin).

• Prevalence: Accounts for approximately $1/3$ of all human body proteins.

• Amino Acid Composition: Nearly $60\%$ Glycine and Proline residues.

• Unique Structure (Tropocollagen): Three left-handed helical chains woven into a right-handed superhelical twist.

  • Glycine: Small side chain, permits the characteristic twist.

  • Proline: Rigid, creates kinks/turns; heavily modified to hydroxyprolyl residues, enabling extensive hydrogen bonding.

• Stability:

  • Extensive hydrogen bonding network (due to hydroxyprolyl groups).

  • Covalent crosslinks between His and Lys residues.

  • Requires high energy to break down, essential for its physiological structural role.