Crystallographic insight into collagen recognition by discoidin domain receptor 2

Structure. 2009 Dec 9;17(12):1573-1581. doi: 10.1016/j.str.2009.10.012.

Abstract

The discoidin domain receptors, DDR1 and DDR2, are widely expressed receptor tyrosine kinases that are activated by triple-helical collagen. They control important aspects of cell behavior and are dysregulated in several human diseases. The major DDR2-binding site in collagens I-III is a GVMGFO motif (O is hydroxyproline) that also binds the matricellular protein SPARC. We have determined the crystal structure of the discoidin domain of human DDR2 bound to a triple-helical collagen peptide. The GVMGFO motifs of two collagen chains are recognized by an amphiphilic pocket delimited by a functionally critical tryptophan residue and a buried salt bridge. Collagen binding results in structural changes of DDR2 surface loops that may be linked to the process of receptor activation. A comparison of the GVMGFO-binding sites of DDR2 and SPARC reveals a striking case of convergent evolution in collagen recognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Evolution
  • Collagen / metabolism*
  • Crystallography, X-Ray
  • Discoidin Domain Receptors
  • Models, Molecular
  • Protein Binding
  • Receptor Protein-Tyrosine Kinases / chemistry
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Mitogen / chemistry
  • Receptors, Mitogen / metabolism*

Substances

  • Receptors, Mitogen
  • Collagen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases