Osteogenesis imperfecta murine: Interaction between type I collagen homotrimers

Types I, II, and III collagens are believed to have evolved from the same h omotrimer ancestor and they have substantial sequence homology, but type I molecules are alpha1(I)(2)alpha2(I) heterotrimers, unlike homotrimeric type s II and III. It is believed that the alpha2(I) chain first appeared in low er vertebrates formation. For instance, spontaneous mutations resulting in nonfunctional alpha2 chains and formation of type I homotrimers cause sever e bone pathology (osteogenesis imperfecta) in humans and in animals. Howeve r, the exact role of the alpha2 chain is not known. Here, we report measure ments of intermolecular forces between collagen helices in native and recon stituted fibers composed of type I homotrimers, heterotrimers and their mix . For comparison, we report forces between type II homotrimers in reconstit uted fibers. In agreement with previous studies, we find that the absence o f the alpha2 chain reduces temperature-favored attraction between collagen helices, either because of the difference in amino acid sequence of the alp ha1 and alpha2 chains or because of more extensive post-translational modif ication of homotrimers. We find that forces between helices in fibers from type I las well as type Il) homotrimers are not sensitive to pH between pH 6 and 7.5, in contrast to type I heterotrimers. Apparently, the effect of p H is related to extra histidine residues present on alpha2 chains but not o n alpha1 chains. Finally, our measurements indicate that the alpha2 chain i s responsible for binding some soluble compound(s), possibly glycosaminogly cans, whose displacement results, e.g., in the loss of tendon crystallinity . The ability of the alpha2 chain to bind non-collagen matrix components ma y be particularly important for bone matrix formation and mineralization. ( C) 2001 Academic Press.