Mutation in cyclophilin B that causes hyperelastosis cutis in american quarter horse does not affect peptidylprolyl cis-trans isomerase activity but shows altered cyclophilin b-protein interactions and affects collagen folding

Yoshihiro Ishikawa, Janice Vranka, Sergei P. Boudko, Elena Pokidysheva, Kazunori Mizuno, Keith Zientek, Douglas R. Keene, Ann M. Rashmir-Raven, Kazuhiro Nagata, Nena J. Winand, Hans Peter Bächinger

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The rate-limiting step of folding of the collagen triple helix is catalyzed by cyclophilin B (CypB). The G6R mutation in cyclophilin B found in the American Quarter Horse leads to autosomal recessive hyperelastosis cutis, also known as hereditary equine regional dermal asthenia. The mutant protein shows small structural changes in the region of the mutation at the side opposite the catalytic domain of CypB. The peptidylprolyl cistrans isomerase activity of the mutant CypB is normal when analyzed in vitro. However, the biosynthesis of type I collagen in affected horse fibroblasts shows a delay in folding and secretion and a decrease in hydroxylysine and glucosyl-galactosyl hydroxylysine. This leads to changes in the structure of collagen fibrils in tendon, similar to those observed in P3H1 null mice. In contrast to cyclophilin B null mice, where little 3-hydroxylation was found in type I collagen, 3-hydroxylation of type I collagen in affected horses is normal. The mutation disrupts the interaction of cyclophilin B with the P-domain of calreticulin, with lysyl hydroxylase 1, and probably other proteins, such as the formation of the P3H1·CypB· cartilage-associated protein complex, resulting in less effective catalysis of the rate-limiting step in collagen folding in the rough endoplasmic reticulum.

Original languageEnglish (US)
Pages (from-to)22253-22265
Number of pages13
JournalJournal of Biological Chemistry
Issue number26
Publication statusPublished - Jun 22 2012
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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