Crystal structure of the extracellular segment of integrin αVβ3
Crystal structure of the extracellular segment of integrin αVβ3
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DOI：
10.1126/science.1064535
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发表时间：
2001-10-12
期刊：
影响因子：
56.9
通讯作者：
Arnaout, MA
中科院分区：
文献类型：
--
作者：
Xiong, JP;Stehle, T;Arnaout, MA
整合素是α β异二聚体受体，其通过与配体的严格调节的相互作用介导二价阳离子依赖性细胞-细胞和细胞-基质粘附。我们已经解决了在3.1埃分辨率的整合素α V β 3的细胞外部分的晶体结构。它的12个结构域组装成一个卵圆形的“头”和两个“尾”。“在晶体中，α V β 3在其尾部的一个定义区域严重弯曲，反映了一种不寻常的灵活性，可能与整合素调节有关。主要的亚基间界面在头部内，在来自alphaV的七叶β-螺旋桨和来自β 3的A结构域之间，并且与G蛋白中的G α/G β界面惊人地相似。β A结构域中的金属离子依赖性粘附位点（MIDAS）被定位为参与由螺旋桨和β A结构域的环形成的配体结合界面。MIDAS与具有潜在调节功能的钙结合位点相邻。
Integrins are alpha beta heterodimeric receptors that mediate divalent cation-dependent cell-cell and cell-matrix adhesion through tightly regulated interactions with ligands. We have solved the crystal structure of the extracellular portion of integrin alphaV beta3 at 3.1 Angstrom resolution. Its 12 domains assemble into an ovoid "head" and two "tails." In the crystal, alphaV beta3 is severely bent at a defined region in its tails, reflecting an unusual flexibility that may be linked to integrin regulation. The main intersubunit interface ties within the head, between a seven-bladed beta -propeller from alphaV and an A domain from beta3, and bears a striking resemblance to the G alpha /G beta interface in G proteins. A metal ion-dependent adhesion site (MIDAS) in the betaA domain is positioned to participate in a ligand-binding interface formed of loops from the propeller and betaA domains. MIDAS ties adjacent to a calcium-binding site with a potential regulatory function.