Abnormal alpha 2-chain in type I collagen from a patient with a form of osteogenesis imperfecta.
Dermal fibroblasts in culture from a woman with a mild to moderate form of osteogenesis imperfecta synthesize two species of the pro alpha 2-chain of type I procollagen. One chain is normal. The abnormal chain has a slightly faster mobility than normal during electrophoresis in sodium dodecyl sulfate polyacrylamide gels. Analysis of cyanogen bromide peptides of the pro alpha-chain, the alpha-chain, and of the mammalian collagenase cleavage products of the pro alpha- and alpha-chains indicates that the abnormality is confined to the alpha 2(I)CB4 fragment and is consistent with loss of a short triple-helical segment. Type I collagen production was decreased, perhaps because the molecules that contained the abnormal chain were unstable, with a resultant alteration in the ratio of type III to type I collagen secreted into culture medium. Collagen fibrils in bone and skin had a normal periodicity but their diameters were 50% of control; the bone matrix was undermineralized. The structural abnormality in the alpha 2(I)-chain in this patient may affect molecular stability, intermolecular interactions, and collagen-mineral relationships that act to decrease the collagen content of tissues and affect the mineralization of bone.
D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D010013:Osteogenesis Imperfecta / Q000378:metabolism*; D011347:Procollagen / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism*
D011347:Procollagen