The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions.
The pseudoactive site of ILK is essential for its binding to alpha-Parvin and localization to focal adhesions.
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ILK的伪活性位点对于它与α-Parvin的结合和与局灶性粘连的定位至关重要。
DOI：
10.1016/j.molcel.2009.11.028
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发表时间：
2009-12-11
期刊：
影响因子：
16
通讯作者：
Qin, Jun
中科院分区：
文献类型：
--
作者：
Fukuda, Koichi;Gupta, Sudhiranjan;Chen, Ka;Wu, Chuanyue;Qin, Jun
整合素连接激酶（ILK）在连接跨膜受体整合素与肌动蛋白细胞骨架，从而调节多种细胞粘附依赖性过程中起着关键作用。ILK的激酶结构域（KD）对其功能是不可或缺的，但其潜在的分子基础仍然是谜。在这里，我们提出了ILK KD的晶体结构结合到其细胞骨架的调节剂，C-末端calponin同源结构域的α-parvin。在保持经典激酶折叠的同时，ILK KD显示出惊人的假活性位点构象。我们表明，而不是执行激酶功能，这种构象特异性识别α-parvin促进ILK有效组装成局灶性粘连。α-parvin结合的ILK KD可以同时接合整联蛋白β胞质尾。因此，这些结果将ILK定义为机械偶联整联蛋白和α-parvin以介导细胞粘附的独特假激酶。他们还强调了激酶折叠的功能多样性及其在介导许多生物过程中的“活性”位点。
Integrin-linked kinase (ILK) plays a pivotal role in connecting transmembrane receptor integrin to the actin cytoskeleton and thereby regulating diverse cell adhesion-dependent processes. The kinase domain (KD) of ILK is indispensable for its function, but the underlying molecular basis remains enigmatic. Here we present the crystal structure of the ILK KD bound to its cytoskeletal regulator, the C-terminal calponin homology domain of α-parvin. While maintaining a canonical kinase fold, the ILK KD displays a striking pseudo-active site conformation. We show that rather than performing the kinase function, this conformation specifically recognizes α-parvin for promoting effective assembly of ILK into focal adhesions. The α-parvin-bound ILK KD can simultaneously engage integrin β cytoplasmic tails. These results thus define ILK as a distinct pseudokinase that mechanically couples integrin and α-parvin for mediating cell adhesion. They also highlight functional diversity of the kinase fold and its “active” site in mediating many biological processes.
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DOI：
10.1073/pnas.0811415106
发表时间：
2008-12-30
影响因子：
11.1
作者：
Chiswell, Brian P.;Zhang, Rong;Calderwood, David A.
通讯作者：
Calderwood, David A.
影响因子：
4.8
作者：
Deng, JT;Van Lierop, JE;Walsh, MP
通讯作者：
Walsh, MP
影响因子：
2.9
作者：
Fischmann, Thierry O.;Smith, Catherine K.;Madison, Vincent S.
通讯作者：
Madison, Vincent S.
影响因子：
3.3
作者：
Attwell, S;Mills, J;Dedhar, S
通讯作者：
Dedhar, S
影响因子：
15
作者：
Cheng, YH;Zhang, YK;McCammon, JA
通讯作者：
McCammon, JA