Mapping the Effect of Gly Mutations in Collagen on α2β1 Integrin Binding.

摘要: The replacement of one Gly in the essential repeating tripeptide sequence type I collagen triple helix results dominant hereditary bone disorder osteogenesis imperfecta. mechanism leading to pathology likely involves misfolding and autophagy, although it has been hypothesized that some mutations interfere with known interactions. Here, effect replacements within nearby integrin binding GFPGER was investigated using a recombinant bacterial system. When six-triplet human containing introduced into collagen-like protein, this chimeric protein bound integrin. Constructs Ser substitutions inserted still formed trypsin-resistant helix, suggesting small local conformational perturbation. two residues prevented cell attachment as predicted from molecular dynamics studies complex. Replacement C-terminal did not affect binding. In contrast, N-terminal sequence, up four triplets away, decreased adhesion. This pattern suggests either an involvement initial or propagation perturbation mutation site. asymmetry biological consequences relative site may relate observed imperfecta near