Structural insights into de novo actin polymerization
Structural insights into de novo actin polymerization
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DOI：
10.1016/j.sbi.2009.12.012
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发表时间：
2010-04-01
影响因子：
6.8
通讯作者：
Dominguez, Roberto
中科院分区：
文献类型：
--
作者：
Dominguez, Roberto
许多细胞功能依赖于快速和局部的肌动蛋白聚合/解聚。然而，由于聚合中间体（小肌动蛋白寡聚体）的不稳定性和肌动蛋白单体结合蛋白的作用，肌动蛋白在细胞中的从头聚合在动力学上是不利的。细胞使用长丝成核和伸长因子来引发和维持聚合。结构生物学开始阐明这些不相关的蛋白质引发聚合、进行调节和介导单体肌动蛋白向肌动蛋白丝转变的不同机制。一个突出的作用是由W结构域，这在这些蛋白质中的一些发生在串联重复，招募多个肌动蛋白亚基。富含Pro的区域也是丰富的，并且介导profilin-actin复合物的结合，这是细胞中聚合活性肌动蛋白的主要来源。纤维成核和延伸因子经常与Rho家族GTP酶相互作用，其传递来自膜受体的信号以调节肌动蛋白细胞骨架重塑。
Many cellular functions depend on rapid and localized actin polymerization/depolymerization. Yet, the de novo polymerization of actin in cells is kinetically unfavorable because of the instability of polymerization intermediates (small actin oligomers) and the actions of actin monomer binding proteins. Cells use filament nucleation and elongation factors to initiate and sustain polymerization. Structural biology is beginning to shed light on the diverse mechanisms by which these unrelated proteins initiate polymerization, undergo regulation, and mediate the transition of monomeric actin onto actin filaments. A prominent role is played by the W domain, which in some of these proteins occurs in tandem repeats that recruit multiple actin subunits. Pro-rich regions are also abundant and mediate the binding of profilin-actin complexes, which are the main source of polymerization competent actin in cells. Filament nucleation and elongation factors frequently interact with Rho-family GTPases, which relay signals from membrane receptors to regulate actin cytoskeleton remodeling.