Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces.
Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces.
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DOI：
10.1016/j.molcel.2008.11.018
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发表时间：
2008-12-26
期刊：
影响因子：
16
通讯作者：
Springer, Timothy A.
中科院分区：
文献类型：
--
作者：
Zhu, Jianghai;Luo, Bing-Hao;Xiao, Tsan;Zhang, Chengzhong;Nishida, Noritaka;Springer, Timothy A.
整联蛋白αIIbβ3的完整胞外域显示出弯曲、闭合、低亲和力构象（β-膝）和连接细胞骨架附着与配体高亲和力的机制。在配体结合之前，在识别位点（包括协同金属离子结合位点（SyMBS））中加载Ca和Mg离子。配体结合镁离子的亲电性在开放构象中增加。β3膝关节穿过β3-PSI和α IIb旋钮之间，将下β腿埋入裂隙中，从裂隙中释放以进行伸展。晶体和EM中的不同整合素分子揭示了在延伸途径上出现的呼吸。施加到延伸的配体-受体复合物的张力稳定了封闭的低亲和力构象。相比之下，一个额外的横向力施加到β亚基，以模拟连接到移动的肌动蛋白丝稳定开放，高亲和力的构象。该机制长距离传播变构，并将整合素的细胞骨架附着偶联到其高亲和力状态。
The complete ectodomain of integrin αIIbβ3 reveals a bent, closed, low-affinity conformation, the β-knee, and a mechanism for linking cytoskeleton attachment to high affinity for ligand. Ca and Mg ions in the recognition site, including the synergistic metal ion binding site (SyMBS), are loaded prior to ligand binding. Electrophilicity of the ligand-binding Mg ion is increased in the open conformation. The β3 knee passes between the β3-PSI and αIIb-knob to bury the lower β-leg in a cleft, from which it is released for extension. Different integrin molecules in crystals and EM reveal breathing that appears on pathway to extension. Tensile force applied to the extended ligand-receptor complex stabilizes the closed, low-affinity conformation. By contrast, an additional lateral force applied to the β subunit to mimic attachment to moving actin filaments stabilizes the open, high-affinity conformation. This mechanism propagates allostery over long distances and couples cytoskeleton attachment of integrins to their high affinity state.
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影响因子：
56.9
作者：
Hu, Ke;Ji, Lin;Waterman-Storer, Clare M.
通讯作者：
Waterman-Storer, Clare M.
影响因子：
2.9
作者：
Astrof, Nathan S.;Salas, Azucena;Springer, Timothy A.
通讯作者：
Springer, Timothy A.
影响因子：
32.4
作者：
Nishida, Noritaka;Xie, Can;Springer, Timothy A.
通讯作者：
Springer, Timothy A.
影响因子：
56.9
作者：
MIYAMOTO, S;AKIYAMA, SK;YAMADA, KM
通讯作者：
YAMADA, KM
DOI：
10.1083/jcb.200404160
发表时间：
2004-12-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim M;Carman CV;Yang W;Salas A;Springer TA
通讯作者：
Springer TA