BiP binds type I procollagen pro alpha chains with mutations in the carboxyl-terminal propeptide synthesized by cells from patients with osteogenesis imperfecta.

摘要: Of 20 fibroblast cell strains from patients with osteogenesis imperfecta (OI), a disease caused by mutations in the genes encoding type I procollagen, three had increased synthesis of BiP (GRP78), an hsp70-related, endoplasmic reticulum-resident protein. All carry unique pro alpha 1(I) chains which impair procollagen chain association. Immunoprecipitation and pulse-chase experiments show that (immunoglobulin heavy chain-binding protein) stably binds these after brief lag. Ascorbate, increases synthesis, content not others. In one strains, is constitutively elevated prior to ascorbate treatment, less inducible. This strain also has relatively high levels GRP94, another stress Pretreating each increase their reduces subsequent ascorbate-mediated induction. 17 other OI examined, variety mutations, was normal. These results suggest induced specific types mutations: ones carboxyl-terminal propeptide interfere The recognition such shows plays role physiological response production some disease-producing abnormal proteins.