Departamento de Biofísica, Instituto de Química Física, Consejo Superior de Investigationes Científicas, Serrano 119, Madrid 28006, Spain.
J Biol Chem. 2010 Jan 8;285(2):1023-31. doi: 10.1074/jbc.M109.050039. Epub 2009 Nov 6.
Integrin alphaIIbbeta3 is the major membrane protein and adhesion receptor at the surface of blood platelets, which after activation plays a key role in platelet plug formation in hemostasis and thrombosis. Small angle neutron scattering (SANS) and shape reconstruction algorithms allowed formation of a low resolution three-dimensional model of whole alphaIIb beta3 in Ca(2+)/detergent solutions. Model projections after 90 degrees rotation along its long axis show an elongated and "arched" form (135 degrees) not observed before and a "handgun" form. This 20-nm-long structure is well defined, despite alphaIIb beta3 multidomain nature and expected segmental flexibility, with the largest region at the top, followed by two narrower and smaller regions at the bottom. Docking of this SANS envelope into the high resolution structure of alphaIIb beta3, reconstructed from crystallographic and NMR data, shows that the solution structure is less constrained, allows tentative assignment of the disposition of the alphaIIb and beta3 subunits and their domains within the model, and points out the structural analogies and differences of the SANS model with the crystallographic models of the recombinant ectodomains of alphaIIb beta3 and alphaV beta3 and with the cryo-electron microscopy model of whole alphaIIb beta3. The ectodomain is in the bent configuration at the top of the model, where alphaIIb and beta3 occupy the concave and convex sides, respectively, at the arched projection, with their bent knees at its apex. It follows the narrower transmembrane region and the cytoplasmic domains at the bottom end. AlphaIIb beta3 aggregated in Mn(2+)/detergent solutions, which impeded to get its SANS model.
整合素 alphaIIbbeta3 是血小板表面的主要膜蛋白和粘附受体，在激活后在止血和血栓形成中血小板栓子形成中发挥关键作用。小角中子散射 (SANS) 和形状重建算法允许在 Ca(2+)/去污剂溶液中形成整个 alphaIIb beta3 的低分辨率三维模型。沿其长轴旋转 90 度后的模型投影显示出以前未观察到的拉长和“拱形”形式（135 度）和“手枪”形式。尽管 alphaIIb beta3 具有多结构域性质和预期的分段灵活性，但这种 20nm 长的结构定义明确，其最大区域位于顶部，其次是底部的两个更窄和更小的区域。将此 SANS 包络物对接入从晶体学和 NMR 数据重建的 alphaIIb beta3 的高分辨率结构中，表明溶液结构的约束较小，允许暂时分配模型中 alphaIIb 和 beta3 亚基及其结构域的位置，并指出 SANS 模型与 alphaIIb beta3 和 alphaV beta3 的重组外域的晶体学模型以及整个 alphaIIb beta3 的冷冻电子显微镜模型的结构相似性和差异。外域在模型顶部的弯曲构象中，其中 alphaIIb 和 beta3 分别占据拱形投影的凹侧和凸侧，其弯曲的膝盖在其顶点。它遵循较窄的跨膜区域和底部末端的细胞质结构域。在 Mn(2+)/去污剂溶液中聚集的 alphaIIb beta3 阻碍了其 SANS 模型的获取。
