Crystal structure of the extracellular segment of integrin αVβ3 in complex with an Arg-Gly-Asp ligand
Crystal structure of the extracellular segment of integrin αVβ3 in complex with an Arg-Gly-Asp ligand
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DOI：
10.1126/science.1069040
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发表时间：
2002-04-05
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
异源二聚体α-整联蛋白与其配体（包含原型Arg-Gly-Asp序列）的二价阳离子依赖性结合的结构基础尚不清楚。与配体的相互作用触发细胞信号传导所需的整合素中的三级和四级结构重排。在这里，我们报告的晶体结构的整合素α V β 3的细胞外部分在复杂的环肽提出的Arg-Gly-Asp序列。配体结合在α V和β 3亚基之间的主要界面处，并与两者进行广泛接触。在配体的存在下观察到三级和四级变化。三级重排发生在β 3的配体结合结构域β A中;在复合物中，β A获得两个阳离子，其中一个直接接触配体Asp，另一个稳定配体结合表面。配体结合诱导α V相对于β 3的取向的微小变化。
The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alphaV and beta3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in betaA, the ligand-binding domain of beta3; in the complex, betaA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alphaV relative to beta3.