The NC2 domain of collagen IX provides chain selection and heterotrimerization

J Biol Chem. 2010 Jul 30;285(31):23721-31. doi: 10.1074/jbc.M110.128405. Epub 2010 May 27.

Abstract

The mechanism of chain selection and trimerization of fibril-associated collagens with interrupted triple helices (FACITs) differs from that of fibrillar collagens that have special C-propeptides. We recently showed that the second carboxyl-terminal non-collagenous domain (NC2) of homotrimeric collagen XIX forms a stable trimer and substantially stabilizes a collagen triple helix attached to either end. We then hypothesized a general trimerizing role for the NC2 domain in other FACITs. Here we analyzed the NC2 domain of human heterotrimeric collagen IX, the only member of FACITs with all three chains encoded by distinct genes. Upon oxidative folding of equimolar amounts of the alpha1, alpha2, and alpha3 chains of NC2, a stable heterotrimer with a disulfide bridge between alpha1 and alpha3 chains is formed. Our experiments show that this heterotrimerization domain can stabilize a short triple helix attached at the carboxyl-terminal end and allows for the proper oxidation of the cystine knot of type III collagen after the short triple helix.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • C-Peptide / chemistry
  • Circular Dichroism
  • Cloning, Molecular
  • Collagen Type IX / chemistry*
  • Dimerization
  • Humans
  • Molecular Sequence Data
  • Oxygen / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid
  • Thermodynamics
  • Thrombin / chemistry

Substances

  • C-Peptide
  • Collagen Type IX
  • Recombinant Proteins
  • Thrombin
  • Oxygen