HSP47 and FKBP65 cooperate in the synthesis of type I procollagen

Hum Mol Genet. 2015 Apr 1;24(7):1918-28. doi: 10.1093/hmg/ddu608. Epub 2014 Dec 15.


Osteogenesis imperfecta (OI) is a genetic disorder that results in low bone mineral density and brittle bones. Most cases result from dominant mutations in the type I procollagen genes, but mutations in a growing number of genes have been identified that produce autosomal recessive forms of the disease. Among these include mutations in the genes SERPINH1 and FKBP10, which encode the type I procollagen chaperones HSP47 and FKBP65, respectively, and predominantly produce a moderately severe form of OI. Little is known about the biochemical consequences of the mutations and how they produce OI. We have identified a new OI mutation in SERPINH1 that results in destabilization and mislocalization of HSP47 and secondarily has similar effects on FKBP65. We found evidence that HSP47 and FKBP65 act cooperatively during posttranslational maturation of type I procollagen and that FKBP65 and HSP47 but fail to properly interact in mutant HSP47 cells. These results thus reveal a common cellular pathway in cases of OI caused by HSP47 and FKBP65 deficiency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Child, Preschool
  • Collagen Type I / biosynthesis*
  • Female
  • HSP47 Heat-Shock Proteins / chemistry
  • HSP47 Heat-Shock Proteins / genetics
  • HSP47 Heat-Shock Proteins / metabolism*
  • Humans
  • Male
  • Molecular Sequence Data
  • Osteogenesis Imperfecta / genetics
  • Osteogenesis Imperfecta / metabolism*
  • Pedigree
  • Procollagen / biosynthesis*
  • Protein Transport
  • Sequence Alignment
  • Tacrolimus Binding Proteins / chemistry
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism*
  • Young Adult


  • Collagen Type I
  • HSP47 Heat-Shock Proteins
  • Procollagen
  • SERPINH1 protein, human
  • Tacrolimus Binding Proteins
  • FKBP10 protein, human