Collagen is the most abundant protein in the human body, providing the structural framework and tensile strength for connective tissues like skin, tendons, and bones. While Type I collagen forms the bulk of large, load-bearing fibers, Type V collagen is a minor, regulatory fibrillar component. This less-abundant protein manages the organization and mechanical properties of the entire extracellular matrix. Its primary role is controlling the assembly of larger collagen fibers, which ultimately dictates the integrity of various tissues.
The Unique Molecular Structure of Collagen V
Type V collagen is formed from three alpha polypeptide chains that assemble into a rope-like triple helix. Unlike Type I collagen, Type V is characterized by multiple isoforms resulting from different combinations of its chains: \(\alpha1(V)\), \(\alpha2(V)\), and \(\alpha3(V)\). The most prevalent form in tissues is the heterotrimer \([\alpha1(V)]_2\alpha2(V)\).
The chains are initially synthesized as precursors called procollagen V, containing non-triple-helical propeptides at the amino (N) and carboxyl (C) ends. These propeptides guide chain alignment before helix formation. Enzymes outside the cell process the procollagen by cleaving the C-propeptide, a necessary step for molecule incorporation into a fiber.
A distinguishing feature is that Type V retains a large portion of the N-terminal propeptide after processing. This retained non-collagenous domain remains exposed on the surface of the growing fiber. This unique architecture is directly linked to its function as a regulator of fiber size.
Regulatory Function in Tissue Architecture
The primary function of Type V collagen is its role as a nucleator for the formation of larger Type I collagen fibers. Type V molecules are incorporated into the core of the developing fiber at the beginning of the assembly process, creating heterotypic fibrils.
Once integrated, the retained N-terminal domain acts as a physical barrier or spacer on the surface of the nascent fiber. This constraint limits the addition of Type I collagen molecules, effectively controlling the final fiber diameter. Reducing Type V collagen leads to fewer, but larger, and structurally abnormal Type I fibers.
For instance, in the cornea, a high concentration of Type V maintains the precise, small, and uniform fiber diameter (around 25 nanometers) essential for transparency. In skin and tendons, this regulation ensures the uniform organization and tensile strength necessary to withstand mechanical stress.
Genetic Disorders Linked to Collagen V Defects
Defects in the genes COL5A1 and COL5A2, which produce the \(\alpha1(V)\) and \(\alpha2(V)\) chains, are the underlying cause of several connective tissue disorders. Mutations in these genes primarily lead to the classical form of Ehlers-Danlos Syndrome (EDS).
Classical EDS is characterized by hyperelastic skin, joint hypermobility, and tissue fragility. These symptoms arise because the genetic defect reduces functional Type V collagen available for fiber assembly. The resulting lack of Type V impairs the nucleation process, leading to the formation of disorganized and unusually large-diameter Type I collagen fibrils.
This faulty organization weakens connective tissue throughout the body. The skin becomes fragile and easily bruised, and the ligaments and tendons lose structural integrity, resulting in joint laxity and frequent dislocations. Defects in Type V collagen have also been implicated in certain corneal dystrophies, where the loss of precise fiber diameter regulation compromises the eye’s structure and clarity.