Xaa-Arg-Gly triplets in the collagen triple helix are dominant binding sites for the molecular chaperone HSP47

J Biol Chem. 2002 Feb 22;277(8):6178-82. doi: 10.1074/jbc.M106497200. Epub 2001 Dec 19.


HSP47 is an essential procollagen-specific molecular chaperone that resides in the endoplasmic reticulum of procollagen-producing cells. Recent advances have revealed that HSP47 recognizes the (Pro-Pro-Gly)(n) sequence but not (Pro-Hyp-Gly)(n) and that HSP47 recognizes the triple-helical conformation. In this study, to better understand the substrate recognition by HSP47, we synthesized various collagen model peptides and examined their interaction with HSP47 in vitro. We found that the Pro-Arg-Gly triplet forms an HSP47-binding site. The HSP47 binding was observed only when Arg residues were incorporated in the Yaa positions of the Xaa-Yaa-Gly triplets. Amino acids in the Xaa position did not largely affect the interaction. The recognition of the Arg residue by HSP47 was specific to its side-chain structure because replacement of the Arg residue by other basic amino acids decreased the affinity to HSP47. The significance of Arg residues in HSP47 binding was further confirmed by using residue-specific chemical modification of types I and III collagen. Our results demonstrate that Xaa-Arg-Gly sequences in the triple-helical procollagen molecule are dominant binding sites for HSP47 and enable us to predict HSP47-binding sites in homotrimeric procollagen molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Arginine
  • Binding Sites
  • Cattle
  • Collagen / chemistry*
  • Collagen / metabolism
  • Collagen Type I / chemistry
  • Collagen Type III / chemistry
  • Glycine
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / metabolism*
  • Kinetics
  • Oligopeptides / chemistry*
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Collagen Type I
  • Collagen Type III
  • Heat-Shock Proteins
  • Oligopeptides
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Collagen
  • Arginine
  • Glycine