Anomalous cysteine in type I collagen. Localisation by chemical cleavage of the protein using 2-nitro-5-thiocyanobenzoic acid and by mismatch analysis of cDNA heteroduplexes

Matrix. 1990 Mar;10(1):20-6. doi: 10.1016/s0934-8832(11)80133-2.

Abstract

A method is presented for the localisation of an anomalous cysteine inside the triple helical domain of type I collagen from a patient affected with Osteogenesis Imperfecta. The chemical cleavage used relies on the specificity and reactivity of the thiol side chain versus 2-nitro-5-thiocyanobenzoic acid, to yield cyanocysteine; in mild alkaline conditions this derivative will undergo the breakdown of its N-side peptide bond. This method could allow a more precise localisation of anomalous cysteine in both type I collagen alpha chains, alpha 1(I) and alpha 2(I), compared to previous analytical methods on CNBr peptides. For the mutant alpha 1(I) chains from a patient affected by Osteogenesis Imperfecta, we found a location of cysteine in the peptide alpha 1(I)CB8, between amino acids 170-200. Biochemical localisation was confirmed by a chemical cleavage method for mismatched cytosines on heteroduplexes obtained after denaturation and annealing of a 233 bp cDNA fragment amplified by PCR from the heterozygote patient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Collagen / analysis*
  • Collagen / genetics
  • Cysteine / analysis*
  • DNA
  • Fibroblasts
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Osteogenesis Imperfecta / metabolism*
  • Polymerase Chain Reaction
  • Skin / analysis*
  • Thiocyanates*

Substances

  • Thiocyanates
  • Collagen
  • DNA
  • Cysteine
  • 2-nitro-5-thiocyanobenzoic acid