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.
Ichikawa
Osamu
O
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Osawa
Masanori
M
Nishida
Noritaka
N
Goshima
Naoki
N
Nomura
Nobuo
N
Shimada
Ichio
I
D001665:Binding Sites; D003094:Collagen / Q000378:metabolism*; D004252:DNA Mutational Analysis; D000070818:Discoidin Domain Receptors; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases
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