Emsley J, King S L, Bergelson J M, Liddington R C
Department of Biochemistry, University of Leicester, Leicester LE1 7RH, United Kingdom.
J Biol Chem. 1997 Nov 7;272(45):28512-7. doi: 10.1074/jbc.272.45.28512.
We have determined the high resolution crystal structure of the I domain from the alpha-subunit of the integrin alpha2beta1, a cell surface adhesion receptor for collagen and the human pathogen echovirus-1. The domain, as expected, adopts the dinucleotide-binding fold, and contains a metal ion-dependent adhesion site motif with bound Mg2+ at the top of the beta-sheet. Comparison with the crystal structures of the leukocyte integrin I domains reveals a new helix (the C-helix) protruding from the metal ion-dependent adhesion site face of the domain which creates a groove centered on the magnesium ion. Modeling of a collagen triple helix into the groove suggests that a glutamic acid side chain from collagen can coordinate the metal ion, and that the C-helix insert is a major determinant of binding specificity. The binding site for echovirus-1 maps to a distinct surface of the alpha2-I domain (one edge of the beta-sheet), consistent with data showing that virus and collagen binding occur by different mechanisms. Comparison with the homologous von Willebrand factor A3 domain, which also binds collagen, suggests that the two domains bind collagen in different ways.
我们已经确定了整合素α2β1的α亚基中I结构域的高分辨率晶体结构，α2β1是一种细胞表面粘附受体，可识别胶原蛋白和人类病原体埃可病毒1。正如预期的那样，该结构域采用二核苷酸结合折叠结构，并且在β折叠的顶部包含一个金属离子依赖性粘附位点基序，其中结合有Mg2+。与白细胞整合素I结构域的晶体结构进行比较，发现该结构域的金属离子依赖性粘附位点面上突出一个新的螺旋（C螺旋），该螺旋在镁离子周围形成一个凹槽。将胶原蛋白三螺旋模型放入该凹槽表明，胶原蛋白的一个谷氨酸侧链可以与金属离子配位，并且C螺旋插入是结合特异性的主要决定因素。埃可病毒1的结合位点定位于α2-I结构域的一个不同表面（β折叠的一条边缘），这与表明病毒和胶原蛋白通过不同机制结合的数据一致。与同样结合胶原蛋白的同源血管性血友病因子A3结构域进行比较，表明这两个结构域以不同方式结合胶原蛋白。
