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Structure. 2009 Dec 9;17(12):1573-81. doi: 10.1016/j.str.2009.10.012.

Crystallographic insight into collagen recognition by discoidin domain receptor 2.

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  • 1Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

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.

PMID:
20004161
[PubMed - indexed for MEDLINE]
PMCID:
PMC2807035
Free PMC Article
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