Structural study of a mutant type I collagen from a patient with lethal osteogenesis imperfecta containing an intramolecular disulfide bond in the triple-helical domain

AbstractWe have built molecular models of collagen type I from a patient with lethal osteogenesis imperfecta incorporating one or two mutant α1(I)-chains which contain a cysteine substituting a glycine near the C-terminal end. In either case, the cysteines can only be accommodated with considerable distortion of the native collagen structure, which disrupts inter-chain contacts. The disturbance of the triple helix is limited to a small local region. This suggests that the most important consequence of the mutation is delayed helix formation leading to overmodification and decreased collagen production, rather than the structural abnormality of the folded molecules, which are only marginally unstable