Collagen is the most abundant protein in the human body, providing the structural scaffolding for virtually all connective tissues, including skin, tendons, and bone. While Type I collagen accounts for the majority of the body’s collagen mass, numerous other types exist, each with a specialized function. Type V collagen is a quantitatively minor yet functionally significant component that plays a foundational role in organizing major connective tissues.
Molecular Structure and Classification
Type V collagen is categorized as a fibril-forming collagen, grouping it with prevalent types like Type I and Type III. Like all collagens, its structure is based on a triple helix formed by three intertwined polypeptide chains, known as alpha chains. The primary form of Type V collagen is a heterotrimer, often composed of two alpha 1(V) chains and one alpha 2(V) chain.
Other variations exist, such as a trimer composed of three alpha 1(V) chains or a heterotrimer incorporating the alpha 3(V) chain. These alpha chains are synthesized from distinct genes: alpha 1(V) is encoded by the COL5A1 gene, alpha 2(V) by COL5A2, and alpha 3(V) by COL5A3. Although structurally similar to major fibrillar collagens, Type V is a quantitative minor collagen, constituting only a small percentage of the total collagen in most tissues.
Distribution in the Human Body
Type V collagen is widely distributed across various organ systems and tissues. It is found in the interstitial matrix of many tissues, often in close proximity to the basement membrane. It is a prominent component of the dermal/epidermal junction in the skin.
Type V collagen is also concentrated in specific structures that require precise fibril organization, such as the cornea of the eye. Furthermore, it is present in the placenta and in tissues like the lungs and bone, where it co-assembles with Type I collagen. This association forms heterotypic fibrils, meaning the fibers are composed of more than one type of collagen.
Essential Regulatory Functions
The primary biological function of Type V collagen is not to provide mechanical support, but to act as a regulator of Type I collagen fibrils. Type V molecules incorporate into Type I fibrils during their assembly in the extracellular space. This process is known as fibrillogenesis, and Type V collagen is thought to be the nucleus, or initial seed, around which Type I collagen begins to aggregate. This nucleation role controls the diameter of the mature collagen fibers. When Type V collagen is present, it limits the lateral growth of the Type I fibers, ensuring they remain thin and uniformly sized.
Tissues that require fine, consistently sized collagen fibers, such as the cornea, have a higher proportion of Type V collagen to Type I. This diameter regulation is important because the mechanical properties of a tissue—its strength, elasticity, and stability—are determined by the size and organization of its collagen fibrils. For instance, the small, uniform diameter of corneal collagen fibrils allows the tissue to be transparent; a lack of Type V regulation leads to large, disorganized fibrils that scatter light, causing opacification.
Clinical Significance and Associated Conditions
Defects in Type V collagen have significant medical consequences, most notably in the connective tissue disorder Ehlers-Danlos Syndrome (EDS). Classical EDS (cEDS) is overwhelmingly caused by mutations in the COL5A1 and COL5A2 genes, which encode the Type V alpha chains. These genetic changes lead to a reduced amount of functional Type V collagen protein being produced. The resulting shortage of Type V collagen impairs the regulatory process of fibrillogenesis, causing the formation of disorganized and abnormally large Type I collagen fibrils.
Clinically, this manifests as the hallmark features of cEDS: soft, highly extensible, and fragile skin, along with generalized joint hypermobility. The poor quality of the collagen scaffolding leads to tissue weakness and the development of atrophic scars following minor trauma. Dysfunctional Type V collagen is also implicated in other conditions, such as defects in the cornea, which can result in a loss of transparency and function. Understanding the precise function of Type V collagen in regulating fiber assembly is central to developing treatments for these connective tissue disorders.