The molecular defect in an autosomal dominant form of osteogenesis imperfecta. Synthesis of type I procollagen containing cysteine in the triple-helical domain of pro-alpha 1(I) chains.

摘要: Abstract Synthesis of procollagen was examined in skin fibroblasts from a patient with moderately severe autosomal dominant form osteogenesis imperfecta. Proteolytic removal the propeptide regions newly synthesized procollagen, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions, revealed presence type I collagen which two alpha 1(I) chains were linked through interchain disulfide bonds. Fragmentation disulfide-bonded dimers vertebrate collagenase and cyanogen bromide demonstrated cysteine residue 1(I)CB8, fragment containing amino acid residues 124-402 chain. Cysteine are not normally found triple-helical domain chains. The heterozygous nature molecular defect resulted formation three kinds trimers: normal pro-alpha(I) chains, trimer one mutant pro-alpha chain 2(I) or trimers to reduce thermal stability protein 2.5 1 degree C, respectively. In addition post-translational overmodification, also cleared more slowly cultured fibroblasts. most likely explanation for these disruptive changes physical secretion is that substituted glycine half patient's