Structure of a highly conserved domain of Rock1 required for Shroom-mediated regulation of cell morphology.
Structure of a highly conserved domain of Rock1 required for Shroom-mediated regulation of cell morphology.
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DOI：
10.1371/journal.pone.0081075
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Vandemark AP
中科院分区：
文献类型：
--
作者：
Mohan S;Das D;Bauer RJ;Heroux A;Zalewski JK;Heber S;Dosunmu-Ogunbi AM;Trakselis MA;Hildebrand JD;Vandemark AP
Rho相关卷曲螺旋蛋白激酶（Rho激酶或Rock）是迄今为止大多数动物细胞中肌动蛋白组织和动力学的明确决定因素。Rock的主要效应物之一是非肌肉肌球蛋白II。Rock的激活导致肌球蛋白II的收缩性增加以及随后的肌动蛋白结构和细胞形态的变化。Rock的调节被认为通过激酶结构域的自身抑制经由激酶的N-末端和C-末端之间的分子内相互作用而发生。这种自我抑制状态可以通过蛋白水解裂解、脂质与C末端附近的普列克底物蛋白同源结构域结合或GTP结合的RhoA与Rock的中央卷曲螺旋区结合来缓解。最近的工作已经确定了蘑菇家族的蛋白质作为一个额外的调节岩石无论是在细胞分布或催化活性的水平或两者兼而有之。蘑菇-岩石复合体在大多数动物中是保守的，并且对于脊椎动物的神经管、眼睛和肠道的形成是必不可少的。为了解决蘑菇和岩石相互作用的机制，我们已经解决了岩石的卷曲螺旋区域的结构，结合蘑菇蛋白。与其他观察结果一致，蘑菇结合结构域是平行卷曲螺旋二聚体。使用生物化学方法，我们已经确定了一个大补丁的残基，有助于Shrm结合。他们的取向表明，可能有两个独立的Shrm结合位点的卷曲螺旋区域的岩石相对的面。最后，我们表明，结合表面是必不可少的岩石与蘑菇共定位和蘑菇介导的细胞形态的变化。
Rho-associated coiled coil containing protein kinase (Rho-kinase or Rock) is a well-defined determinant of actin organization and dynamics in most animal cells characterized to date. One of the primary effectors of Rock is non-muscle myosin II. Activation of Rock results in increased contractility of myosin II and subsequent changes in actin architecture and cell morphology. The regulation of Rock is thought to occur via autoinhibition of the kinase domain via intramolecular interactions between the N-terminus and the C-terminus of the kinase. This autoinhibited state can be relieved via proteolytic cleavage, binding of lipids to a Pleckstrin Homology domain near the C-terminus, or binding of GTP-bound RhoA to the central coiled-coil region of Rock. Recent work has identified the Shroom family of proteins as an additional regulator of Rock either at the level of cellular distribution or catalytic activity or both. The Shroom-Rock complex is conserved in most animals and is essential for the formation of the neural tube, eye, and gut in vertebrates. To address the mechanism by which Shroom and Rock interact, we have solved the structure of the coiled-coil region of Rock that binds to Shroom proteins. Consistent with other observations, the Shroom binding domain is a parallel coiled-coil dimer. Using biochemical approaches, we have identified a large patch of residues that contribute to Shrm binding. Their orientation suggests that there may be two independent Shrm binding sites on opposing faces of the coiled-coil region of Rock. Finally, we show that the binding surface is essential for Rock colocalization with Shroom and for Shroom-mediated changes in cell morphology.
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影响因子：
4.8
作者：
Fujisawa, K;Fujita, A;Narumiya, S
通讯作者：
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影响因子：
4.8
作者：
Dietz, Megan L.;Bernaciak, Teresa M.;Hildebrand, Jeffrey D.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
Cowtan, K
影响因子：
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作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH