Crystallographic insight into collagen recognition by discoidin domain receptor 2.

Article Details

Citation

Carafoli F, Bihan D, Stathopoulos S, Konitsiotis AD, Kvansakul M, Farndale RW, Leitinger B, Hohenester E

Crystallographic insight into collagen recognition by discoidin domain receptor 2.

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

PubMed ID
20004161 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Discoidin domain-containing receptor 2Q16832Details