Structural insights into how the MIDAS ion stabilizes integrin binding to an RGD peptide under force
Structural insights into how the MIDAS ion stabilizes integrin binding to an RGD peptide under force
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DOI：
10.1016/j.str.2004.09.009
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发表时间：
2004-11-01
期刊：
影响因子：
5.7
通讯作者：
Vogel, V
中科院分区：
文献类型：
--
作者：
Craig, D;Gao, M;Vogel, V
整合素 alpha(v)beta(3) 通过三肽 Arg-Gly-Asp (RGD) 与细胞外基质蛋白结合，形成浅缝隙而不是深结合袋。 RGD-alpha(v)beta(3) 复合物如何抵抗机械力解离的动态图是从转向分子动力学 (SMD) 模拟中得出的，其中主力峰值与 Asp(RGD) 和 MIDAS 离子之间接触的破坏相关。 SMD 预测，RGD-alpha(v)beta(3) 复合物通过与二价 MIDAS 离子紧密配位的单个水分子来稳定解离，从而阻止自由水分子进入最关键的受力相互作用。 MIDAS 基序是许多其他含有系统发育上古老的冯维勒布兰德 A (vWA) 结构域的蛋白质所共有的。与 MIDAS 离子紧密配合的单个水分子的功能作用可能反映了通过二价阳离子稳定蛋白质-蛋白质粘附以抵抗细胞衍生力的一般策略。
Integrin alpha(v)beta(3) binds to extracellular matrix proteins through the tripeptide Arg-Gly-Asp (RGD), forming a shallow crevice rather than a deep binding pocket. A dynamic picture of how the RGD-alpha(v)beta(3) complex resists dissociation by mechanical force is derived here from steered molecular dynamic (SMD) simulations in which the major force peak correlates with the breaking of the contact between Asp(RGD) and the MIDAS ion. SMD predicts that the RGD-alpha(v)beta(3) complex is stabilized from dissociation by a single water molecule tightly coordinated to the divalent MIDAS ion, thereby blocking access of free water molecules to the most critical force-bearing interaction. The MIDAS motif is common to many other proteins that contain the phylogenetically ancient von Willebrand A (vWA) domain. The functional role of single water molecules tightly coordinated to the MIDAS ion might reflect a general strategy for the stabilization of protein-protein adhesion against cell-derived forces through divalent cations.