Substitutions for arginine at position 780 in triple helical domain of the α1(I) chain alter folding of the type I procollagen molecule and cause osteogenesis imperfecta.

ABSTRACT: OI is a clinically and genetically heterogeneous disorder characterized by bone fragility. More than 90% of patients are heterozygous for mutations in type I collagen genes, COL1A1 and COL1A2, and a common mutation is substitution for an obligatory glycine in the triple helical Gly-X-Y repeats. Few non-glycine substitutions in the triple helical domain have been reported; most result in Y-position substitutions of arginine by cysteine. Here, we investigated leucine and cysteine substitutions for one Y-position arginine, p.Arg958 (Arg780 in the triple helical domain) of proα1(I) chains that cause mild OI. We compared their effects with two substitutions for glycine located in close proximity. Like substitutions for glycine, those for arginine reduced the denaturation temperature of the whol

SUBMITTER: Makareeva E 

PROVIDER: S-EPMC6039012 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature