Three-dimensional EM structure of the ectodomain of integrin {alpha}V{beta}3 in a complex with fibronectin.
Three-dimensional EM structure of the ectodomain of integrin {alpha}V{beta}3 in a complex with fibronectin.
复制标题
整合素{alpha} v {beta} 3的三维EM结构与纤连蛋白的复合物中。
DOI：
10.1083/jcb.200410068
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发表时间：
2005-03-28
影响因子：
7.8
通讯作者：
Yeager, Mark
中科院分区：
文献类型：
--
作者：
Adair, Brian D;Xiong, Jian-Ping;Maddock, Catherine;Goodman, Simon L;Arnaout, M Amin;Yeager, Mark
整合素是αβ异二聚体细胞表面受体，其通过结合细胞外和细胞质配体介导跨膜信号传导。整联蛋白αVβ3的胞外域以弯曲、卷曲的构象结晶，被认为是无活性的（不能结合溶液中的生理配体），除非通过激活刺激完全延伸。我们生成了Mn 2+结合的αVβ3胞外域与含有III型结构域7至10和EDB结构域的纤连蛋白（FN）片段（FN 7-EDB-10）的稳定可溶性复合物。使用透射电子显微镜和单颗粒图像分析来确定该复合物的三维结构。大多数αVβ3颗粒，无论是未配体的还是FN结合的，都显示出紧凑的三角形形状。比较无配体和FN结合的αVβ3的差异图显示，密度可以容纳β3配体结合位点附近的含RGD的FN 10，而FN 9恰好邻近αV的协同位点结合区。我们的结论是，αVβ3的胞外域表现出一种弯曲的构象，能够在溶液中稳定地结合生理配体。
Integrins are αβ heterodimeric cell surface receptors that mediate transmembrane signaling by binding extracellular and cytoplasmic ligands. The ectodomain of integrin αVβ3 crystallizes in a bent, genuflexed conformation considered to be inactive (unable to bind physiological ligands in solution) unless it is fully extended by activating stimuli. We generated a stable, soluble complex of the Mn2+-bound αVβ3 ectodomain with a fragment of fibronectin (FN) containing type III domains 7 to 10 and the EDB domain (FN7-EDB-10). Transmission electron microscopy and single particle image analysis were used to determine the three-dimensional structure of this complex. Most αVβ3 particles, whether unliganded or FN-bound, displayed compact, triangular shapes. A difference map comparing ligand-free and FN-bound αVβ3 revealed density that could accommodate the RGD-containing FN10 in proximity to the ligand-binding site of β3, with FN9 just adjacent to the synergy site binding region of αV. We conclude that the ectodomain of αVβ3 manifests a bent conformation that is capable of stably binding a physiological ligand in solution.