relate the structures of collagen molecules and collagen fibres to their function

Proteins – Collagen

Learning Objective

Relate the structures of collagen molecules and collagen fibres to their biological function, using the terminology required by the Cambridge International AS & A‑Level Biology syllabus (primary, secondary, tertiary, quaternary structure; fibrous protein; supramolecular structure).

Collagen as a Fibrous Protein

• Collagen is the principal fibrous protein in mammals – insoluble in water and specialised for structural support.
• It accounts for ≈30 % of total body protein and provides tensile strength to skin, tendon, bone, cartilage, ligaments and the extracellular matrix.

Major Types of Collagen (examples required by the syllabus)

Collagen Biosynthesis (overview)

1. Ribosomal translation of pre‑pro‑collagen in the rough ER; a signal peptide directs the nascent chain into the lumen.
2. Post‑translational modifications (still in the ER):
   • Hydroxylation of proline and lysine residues – catalysed by prolyl‑ and lysyl‑hydroxylases; requires vitamin C as a co‑factor.
   • Glycosylation of specific hydroxy‑lysine residues.
3. Triple‑helix formation – three modified α‑chains align in a staggered (Gly‑X‑Y)_n register and fold into a right‑handed triple helix (procollagen).
4. Transport to the Golgi, packaging into secretory vesicles and exocytosis into the extracellular space.
5. Extracellular processing:
   • Propeptide cleavage by specific proteinases yields mature collagen molecules.
   • Lysyl‑oxidase oxidises selected lysine residues to aldehydes, enabling covalent cross‑links.
6. Fibril assembly – collagen molecules self‑assemble laterally into staggered fibrils; fibrils aggregate into fibres and, in tendons, into fascicles.

Structural Hierarchy and Functional Consequences

1. Primary Structure

Definition (syllabus): The linear sequence of amino‑acid residues in a polypeptide.

• Repeating tripeptide motif (Gly‑X‑Y)_n where:
  • Gly = glycine – the only residue small enough to fit at the centre of the triple helix.
  • X is frequently proline.
  • Y is frequently hydroxyproline (formed by vitamin C‑dependent hydroxylation).
• Glycine at every third position allows three α‑chains to interdigitate tightly, a prerequisite for helix stability.

2. Secondary Structure – Triple Helix

Definition (syllabus): Regular folding of the polypeptide chain(s) into a locally ordered shape.

• Three left‑handed poly‑proline II helices wrap around one another to give a right‑handed super‑helix (the collagen molecule).
• Stabilising interactions:
  1. Inter‑chain hydrogen bonds: carbonyl O of Gly in one chain ↔ amide H of X or Y in an adjacent chain.
  2. Hydroxyproline stabilises the helix by forming additional H‑bonds with water molecules.
• Dimensions: ≈300 nm long, ≈1.5 nm in diameter – a rigid, rod‑like molecule.
• Functional outcome: resistance to unwinding and to proteolytic attack; ideal for load‑bearing.

3. Tertiary / Quaternary Structure – Fibril Formation

Definition (syllabus): The three‑dimensional arrangement of one (tertiary) or several (quaternary) polypeptide chains.

• Collagen molecules pack laterally in a staggered array to form **fibrils**.
• Each molecule is offset by ~67 nm relative to its neighbours, creating the characteristic **D‑periodic banding** seen in electron micrographs.
• Cross‑linking:
  • Lysyl‑oxidase converts specific lysine residues to aldehydes, which then form covalent intermolecular cross‑links.
  • Cross‑links give fibrils high tensile strength and control elasticity.

4. Supramolecular Organisation – Collagen Fibre

Definition (syllabus): The highest level of protein structure, where several quaternary assemblies associate.

• Fibrils laterally aggregate and are further bundled into **collagen fibres**; groups of fibres form fascicles in tendons and ligaments.
• Resulting functional properties:
  • Tensile strength: Load is transmitted along the long axis of the fibre; the tightly packed, cross‑linked fibrils resist pulling apart.
  • Flexibility: Limited sliding of fibrils against each other permits stretch without rupture.
  • Resistance to tearing: The staggered D‑period distributes stress over many molecules.

Structure–Function Summary

Clinical Relevance (syllabus examples)

• Scurvy: Vitamin C deficiency prevents hydroxylation of proline and lysine → unstable triple helix → weak connective tissue, bleeding gums, poor wound healing.
• Osteogenesis imperfecta: Mutations in the Gly‑X‑Y motif of type I collagen → malformed triple helices → brittle bones.
• Ehlers‑Danlos syndrome (some types): Defects in lysyl‑hydroxylase or collagen‑processing enzymes → reduced cross‑linking → hyper‑flexible joints and fragile skin.
• Diabetes‑related non‑enzymatic glycation: Excessive cross‑links form spontaneously, decreasing tissue elasticity and contributing to vascular complications.

Suggested Diagram for Classroom Use

A schematic hierarchy illustrating: amino‑acid sequence → triple‑helical collagen molecule → staggered fibril with D‑period → macroscopic fibre/fascicle. Labels should include glycine residues, hydroxyproline, the 67 nm offset, and covalent cross‑links.

Summary Points

1. Collagen is a fibrous, water‑insoluble protein whose Gly‑X‑Y primary structure is essential for forming a tight triple helix.
2. The triple helix creates a rigid, rod‑like molecule that can pack into staggered fibrils.
3. Enzymatic lysyl‑oxidase cross‑links between fibrils give collagen fibres their remarkable tensile strength and controlled elasticity.
4. The hierarchical organisation (primary → secondary → tertiary/quaternary → supramolecular fibre) directly explains collagen’s role in supporting skin, tendons, bone, cartilage and other connective tissues.