Structural basis of the collagen-binding mode of discoidin domain receptor 2
Structural basis of the collagen-binding mode of discoidin domain receptor 2
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DOI：
10.1038/sj.emboj.7601833
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发表时间：
2007-09-19
期刊：
影响因子：
11.4
通讯作者：
Shimada, Ichio
中科院分区：
文献类型：
--
作者：
Ichikawa, Osamu;Osawa, Masanori;Shimada, Ichio
盘状肽结构域受体（DDR）是一种细胞表面受体酪氨酸激酶，通过其盘状肽（DS）结构域与纤维胶原结合而激活。在此，我们确定了DDR2中DS结构域（DDR2- DS结构域）的NMR结构，并通过转移交叉饱和实验确定了与纤维胶原的结合位点。DDR2- DS结构域结构采用由八条β-链组成的扭曲的卷曲折叠。胶原结合位点形成于环间沟，由疏水残基包围的带电残基组成。胶原结合位点的表面特征表明DDR2- DS结构域识别纤维状胶原上的特定位点。本研究为DDR2- DS结构域的胶原结合模式提供了分子基础.
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.