On the Interaction Between Human IQGAP1 and Actin.
On the Interaction Between Human IQGAP1 and Actin.
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DOI：
10.2174/0929866523666160204123331
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发表时间：
2016-03
影响因子：
1.6
通讯作者：
Damian J. Magill;Elaine Hamilton;S. Shirran;C. Botting;D. Timson
中科院分区：
文献类型：
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作者：
Damian J. Magill;Elaine Hamilton;S. Shirran;C. Botting;D. Timson
IQGAP是整合来自各种来源的信号并在细胞骨架上传递这些信号的真核蛋白。了解它们是如何做到这一点的需要蛋白质之间界面的信息。在此，显示人IQGAP 1（CHD 1）的钙调蛋白同源结构域可以与α-肌动蛋白交联。相互作用的化学计量比为1：1。构建了该复合物的分子模型，生物信息学分析预测，该相互作用可能涉及α-actin的Lys-240和CHD 1的Glu-30之间的静电相互作用。预计这些残基是可接近的，并且不参与许多蛋白质内相互作用;因此它们可用于与结合伴侣相互作用。它们都位于蛋白质中被预测为柔性和无序的区域;信号分子之间的相互作用通常涉及柔性，无序区域。CHD 1中预测的结合区域在许多真核IQGAP样蛋白中是非常保守的。在某些情况下（例如盘基网柄藻和酿酒酵母），蛋白质序列保守性较弱，但分子模拟显示，在柔性N-末端的带电极性残基区域在结构上很保守。因此，我们得出结论，IQGAP 1样蛋白的钙调蛋白同源结构域相互作用最初通过静电相互作用确定这里，可能有随后的构象变化，形成最终的复合物。
IQGAPs are eukaryotic proteins which integrate signals from various sources and pass these on the cytoskeleton. Understanding how they do this requires information on the interfaces between the proteins. Here, it is shown that the calponin homology domain of human IQGAP1 (CHD1) can be crosslinked with α-actin. The stoichiometry of the interaction was 1:1. A molecular model was built of the complex and associated bioinformatics analyses predicted that the interaction is likely to involve an electrostatic interaction between Lys-240 of α-actin and Glu-30 of CHD1. These residues are predicted to be accessible and are not involved in many intra-protein interactions; they are thus available for interaction with binding partners. They are both located in regions of the proteins which are predicted to be flexible and disordered; interactions between signalling molecules often involve flexible, disordered regions. The predicted binding region in CHD1 is well conserved in many eukaryotic IQGAP-like proteins. In some cases (e.g Dictyostelium discoideum and Saccharomyces cerevisiae) protein sequence conservation is weak, but molecular modelling reveals that a region of charged, polar residues in a flexible N-terminus is structurally well conserved. Therefore we conclude that the calponin homology domains of IQGAP1-like proteins interact initially through the electrostatic interaction identified here and that there may be subsequent conformational changes to form the final complex.