2. Academic Validation
  3. Crystallographic insight into collagen recognition by discoidin domain receptor 2

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.
Federico Carafoli 1,  Dominique Bihan 2,  Stavros Stathopoulos 3,  Antonios D Konitsiotis 3,  Marc Kvansakul 1,  Richard W Farndale 2,  Birgit Leitinger 3,  Erhard Hohenester 4
Affiliations

Affiliations

  • 1 Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
  • 2 Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK.
  • 3 Division of National Heart and Lung Institute, Imperial College London, London SW7 2AZ, UK.
  • 4 Department of Life Sciences, Imperial College London, London SW7 2AZ, UK. Electronic address: [email protected].
PMID: 20004161 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.

Figures