A SINGLE BASE MUTATION THAT CONVERTS GLYCINE-907 OF THE ALPHA-2(I) CHAIN OF TYPE-I PROCOLLAGEN TO ASPARTATE IN A LETHAL VARIANT OF OSTEOGENESIS IMPERFECTA - THE SINGLE AMINO-ACID SUBSTITUTION NEAR THE CARBOXYL TERMINUS DESTABILIZES THE WHOLE TRIPLE HELIX

Google Scholar
  • 15 February 1989
    • journal article
    • research article
    • Vol. 264  (5) , 3002-3006
Abstract
Type I procollagen was examined in cultured skin fibroblasts from a patient with a lethal variant of osteogenesis imperfecta. About half of the pro-.alpha. chains were post-translationally overmodified and had a decreased thermal stability. The vertebrate collagenase A fragment had a normal thermal stability, but the B fragment had a decreased thermal stability. Therefore, there was a change in primary structure in amino acids 776-1014 of either the .alpha.1(I) or .alpha.2(I) chain. Three of five cDNA clones for the .alpha.2(I) chain contained a single-base substitution of an A for a G that converted the codon for glycine at amino acid position 907 to aspartate. Complete nucleotide sequencing of bases coding for amino acids 776 to 1014 of the .alpha.2(I) chain was carried out in one cDNA clone that contained the mutation in the glycine codon and in one that did not. Also, nucleotide sequencing was performed of bases coding for amino acids 776-1014 of the .alpha.1(I) chain in seven independent cDNA clones. No other mutations were found. Therefore, the single base substitution that converts glycine 907 in the .alpha.2(I) chain to aspartate is solely responsible for the decreased thermal stability of the type I procollagen synthesized by the proband''s fibroblasts. Also, glycine 907 of the .alpha.2(I) chain is an important component of a cooperative block that determines the melting temperature of the whole molecule.

This publication has 28 references indexed in Scilit: