Structures of the αL I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation
Structures of the αL I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation
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DOI：
10.1016/s0092-8674(02)01257-6
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发表时间：
2003-01-10
期刊：
影响因子：
64.5
通讯作者：
Springer, TA
中科院分区：
文献类型：
--
作者：
Shimaoka, M;Xiao, T;Springer, TA
与 Ig 超家族配体 ICAM-1 结合的整合素 αLβ2 I 结构域的结构揭示了开放配体结合构象和整合素-IgSF 界面的第一个例子。 I 结构域 Mg2+ 直接协调 ICAM-1 的 Glu-34，并且 I 结构域残基 Glu-241 的剧烈摆动能够形成关键的盐桥。高亲和力和中度亲和力突变体 I 结构域的配体和未配体结构表明，配体结合可以诱导 alphaL I 结构域的构象变化，并且变构信号可以将闭合构象转化为中间或开放构象，而无需配体结合。通过引入二硫键向下拉 C 端 α7 螺旋，使 β6-α7 环棘轮进入闭合、中间和开放构象的三个不同位置，亲和力逐渐增加。
The structure of the I domain of integrin alphaLbeta2 bound to the Ig superfamily ligand ICAM-1 reveals the open ligand binding conformation and the first example of an integrin-IgSF interface. The I domain Mg2+ directly coordinates Glu-34 of ICAM-1, and a dramatic swing of I domain residue Glu-241 enables a critical salt bridge. Liganded and unliganded structures for both high- and intermediate-affinity mutant I domains reveal that ligand binding can induce conformational change in the alphaL I domain and that allosteric signals can convert the closed conformation to intermediate or open conformations without ligand binding. Pulling down on the C-terminal alpha7 helix with introduced disulfide bonds ratchets the beta6-alpha7 loop into three different positions in the closed, intermediate, and open conformations, with a progressive increase in affinity.