Understanding the role of the G-actin-binding domain of Ena/VASP in actin assembly
Understanding the role of the G-actin-binding domain of Ena/VASP in actin assembly
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DOI：
10.1016/j.jsb.2006.01.012
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发表时间：
2006-08-01
影响因子：
3
通讯作者：
Dominguez, Roberto
中科院分区：
文献类型：
--
作者：
Chereau, David;Dominguez, Roberto
Ena/VASP和WASP蛋白家族在肌动蛋白细胞骨架重塑中发挥不同的作用。Ena/VASP与肌动蛋白丝的伸长有关，而WASP在Arp 2/3复合物介导的丝成核和分支中起作用。控制这两个过程的分子机制才刚刚出现。Ena/VASP和WASP都是多结构域蛋白。它们都存在多聚脯氨酸区，其介导前纤维蛋白-肌动蛋白的结合，随后是WASP-同源2（WH 2）型的G-肌动蛋白结合（GAB）结构域。然而，Ena/VASP的WH 2与WASP的WH 2有些不同，并且表征不佳。在这里，我们证明，这WH 2结合profilin-actin具有更高的亲和力比单独的肌动蛋白。结果是一致的模型，其中亲和力的变构调节驱动的过渡profilin-actin从聚Pro区域的WH 2，然后到倒刺的长丝在伸长的结束。因此，在Ena/VASP中的WH 2的功能似乎是“加工”profilin-actin，以便将其掺入到生长的细丝的倒刺末端。在新纳入的肌动蛋白亚基的构象变化，无论是从核苷酸水解或从G-到F-肌动蛋白的过渡，可以作为一个“传感器”的Ena/VASP的进行性步进。保守域体系结构表明WASP可以类似地工作。(c)2006年爱思唯尔公司All rights reserved.
The Ena/VASP and WASP family of proteins play distinct roles in actin cytoskeleton remodeling. Ena/VASP is linked to actin filament elongation, whereas WASP plays a role in filament nucleation and branching mediated by Arp2/3 complex. The molecular mechanisms controlling both processes are only emerging. Both Ena/VASP and WASP are multidomain proteins. They both present poly-Pro regions, which mediate the binding of profilin-actin, followed by G-actin-binding (GAB) domains of the WASP-homology 2 (WH2) type. However, the WH2 of Ena/VASP is somewhat different from that of WASP, and has been poorly characterized. Here we demonstrate that this WH2 binds profilin-actin with higher affinity than actin alone. The results are consistent with a model whereby allosteric modulation of affinity drives the transition of profilin-actin from the poly-Pro region to the WH2 and then to the barbed end of the filament during elongation. Therefore, the function of the WH2 in Ena/VASP appears to be to "process" profilin-actin for its incorporation at the barbed end of the growing filament. Conformational changes in the newly incorporated actin subunit, resulting either from nucleotide hydrolysis or from the G- to F-actin transition, may serve as a "sensor" for the processive stepping of Ena/VASP. Conserved domain architecture suggests that WASP may work similarly. (c) 2006 Elsevier Inc. All rights reserved.