Structural basis of the collagen-binding mode of discoidin domain receptor 2

Discoidin domain receptor ( DDR) is a cell- surface receptor tyrosine kinase activated by the binding of its discoidin ( DS) domain to fibrillar collagen. Here, we have determined the NMR structure of the DS domain in DDR2 ( DDR2- DS domain), and identified the binding site to fibrillar collagen by transferred cross- saturation experiments. The DDR2- DS domain structure adopts a distorted jellyroll fold, consisting of eight beta-strands. The collagen-binding site is formed at the interloop trench, consisting of charged residues surrounded by hydrophobic residues. The surface profile of the collagen- binding site suggests that the DDR2- DS domain recognizes specific sites on fibrillar collagen. This study provides a molecular basis for the collagen- binding mode of the DDR2- DS domain.