Control of heterotypic fibril formation by collages V is determined by chain stoichiometry

Although the collagen V heterotrimer is known to be involved in the control of fibril assembly, the role of the homotrimer in fibrillar organization h as not yet been examined. Here, the production of substantial amounts of re combinant collagen V homotrimer has allowed a detailed study of its role in homotypic and heterotypic fibril formation. After removal of terminal regi ons by pepsin digestion, both the collagen V heterotrimer and homotrimer fo rmed thin homotypic fibrils, thus showing that diameter limitation is at le ast in part an intrinsic property of the collagen V triple helix. When mixe d with collagen I, however, various complementary approaches indicated that the collagen V heterotrimer and homotrimer exerted different effects in he terotypic fibril formation. Unlike the heterotrimer, which was buried in th e fibril interior, the homotrimer was localized as thin filamentous structu res at the surface of wide collagen I fibrils and did not regulate fibril a ssembly. Its localization at the fibril surface suggests that the homotrime r can act as a molecular linker between collagen fibrils or macromolecules in the extracellular matrix or both. Thus, depending on their respective di stribution in tissues, the different collagen V isoforms might fulfill spec ific biological functions.