Actin filament nucleation and elongation factors--structure-function relationships.

Actin filament nucleation and elongation factors--structure-function relationships.
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DOI:
10.3109/10409230903277340
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发表时间:
2009-11
影响因子:
6.5
通讯作者:
Dominguez R
Dominguez R
中科院分区:
生物学2区
文献类型:
--
作者:
Dominguez R

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细胞内肌动蛋白丝的自发和不受调节的聚合被肌动蛋白单体结合蛋白如profilin和Tβ4抑制。真核细胞和某些病原体使用细丝成核剂来稳定肌动蛋白聚合核,其形成是限速的。已知的细丝成核剂包括Arp 2/3复合物及其大家族的成核促进因子(NPF)、formins、Spire、Cobl、VopL/VopF、TARP和Lmod。这些分子控制聚合的时间和位置,并且另外影响它们产生的肌动蛋白网络的结构。纤维成核剂通常是不相关的,但除了formins,它们都使用WASP同源2结构域(WH 2或W),一个小而多功能的肌动蛋白结合基序,与肌动蛋白相互作用。在Spire、Cobl和VopL/VopF中发现的一种常见结构由串联的W结构域组成,其结合三到四个肌动蛋白亚基以形成细胞核。结构上的考虑表明,NPFs-Arp 2/3复合物也可以被看作是一种特殊形式的串联W-基成核剂。形成蛋白是独特的,因为它们使用形成蛋白同源2(FH 2)结构域与肌动蛋白相互作用,并且不仅促进成核,而且促进进行性倒刺末端延伸。相比之下,W-基成核剂之间的延伸功能已被“外包”给一个专门的蛋白质家族,伊娃/VASP,其与WASP家族NPF相关。
The spontaneous and unregulated polymerization of actin filaments is inhibited in cells by actin monomer-binding proteins such as profilin and Tβ4. Eukaryotic cells and certain pathogens use filament nucleators to stabilize actin polymerization nuclei, whose formation is rate-limiting. Known filament nucleators include the Arp2/3 complex and its large family of Nucleation Promoting Factors (NPFs), formins, Spire, Cobl, VopL/VopF, TARP and Lmod. These molecules control the time and location for polymerization, and additionally influence the structures of the actin networks that they generate. Filament nucleators are generally unrelated, but with the exception of formins they all use the WASP-Homology 2 domain (WH2 or W), a small and versatile actin-binding motif, for interaction with actin. A common architecture, found in Spire, Cobl and VopL/VopF, consists of tandem W domains that bind three to four actin subunits to form a nucleus. Structural considerations suggest that NPFs-Arp2/3 complex can also be viewed as a specialized form of tandem W-based nucleator. Formins are unique in that they use the formin-homology 2 (FH2) domain for interaction with actin and promote not only nucleation, but also processive barbed end elongation. In contrast, the elongation function among W-based nucleators has been “outsourced” to a dedicated family of proteins, Eva/VASP, which are related to WASP-family NPFs.
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