Activation of Arp2/3 complex: addition of the first subunit of the new filament by a WASP protein triggers rapid ATP hydrolysis on Arp2.
Activation of Arp2/3 complex: addition of the first subunit of the new filament by a WASP protein triggers rapid ATP hydrolysis on Arp2.
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DOI：
10.1371/journal.pbio.0020091
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发表时间：
2004-04
期刊：
影响因子：
9.8
通讯作者：
Mullins RD
中科院分区：
文献类型：
--
作者：
Dayel MJ;Mullins RD
响应于WASP家族蛋白的激活，Arp 2/3复合物从预先存在的细丝的侧面成核新的肌动蛋白细丝。WASP家族蛋白的Arp 2/3激活（VCA）区域结合Arp 2/3复合物和肌动蛋白单体，并且Arp 2/3复合物的Arp 2和Arp 3亚基结合ATP。我们发现，Arp 2水解ATP迅速-没有检测滞后-成核后的一个新的肌动蛋白丝。丝状肌动蛋白和VCA一起不刺激Arp 2/3复合物上的ATP水解，在没有VCA的情况下单体和丝状肌动蛋白也不刺激ATP水解。肌动蛋白单体绑定到海洋大环内酯Latrunculin B不破坏，但在鬼笔环肽稳定的肌动蛋白丝和VCA的存在下，他们刺激快速ATP水解Arp 2。这些数据表明，ATP水解的Arp 2/3复合物的刺激与一个单一的肌动蛋白单体的相互作用，并协调VCA的相互作用。我们发现，由Arp 2/3复合物（即使在没有VCA的情况下也会发生）对细丝尖端的封盖也会刺激Arp 2上的快速ATP水解，确定刺激ATP水解的肌动蛋白单体为子细丝尖端的第一个单体。我们的结论是，WASP家族VCA域激活Arp 2/3复合物驱动其与一个单一的传统肌动蛋白单体的相互作用，形成一个Arp 2-Arp 3-肌动蛋白核。这个肌动蛋白单体成为新的子丝的第一个单体。本文提供了肌动蛋白丝形成的生物化学和生物物理学基础，这是细胞形状和运动所必需的
In response to activation by WASP-family proteins, the Arp2/3 complex nucleates new actin filaments from the sides of preexisting filaments. The Arp2/3-activating (VCA) region of WASP-family proteins binds both the Arp2/3 complex and an actin monomer and the Arp2 and Arp3 subunits of the Arp2/3 complex bind ATP. We show that Arp2 hydrolyzes ATP rapidly—with no detectable lag—upon nucleation of a new actin filament. Filamentous actin and VCA together do not stimulate ATP hydrolysis on the Arp2/3 complex, nor do monomeric and filamentous actin in the absence of VCA. Actin monomers bound to the marine macrolide Latrunculin B do not polymerize, but in the presence of phalloidin-stabilized actin filaments and VCA, they stimulate rapid ATP hydrolysis on Arp2. These data suggest that ATP hydrolysis on the Arp2/3 complex is stimulated by interaction with a single actin monomer and that the interaction is coordinated by VCA. We show that capping of filament pointed ends by the Arp2/3 complex (which occurs even in the absence of VCA) also stimulates rapid ATP hydrolysis on Arp2, identifying the actin monomer that stimulates ATP hydrolysis as the first monomer at the pointed end of the daughter filament. We conclude that WASP-family VCA domains activate the Arp2/3 complex by driving its interaction with a single conventional actin monomer to form an Arp2–Arp3–actin nucleus. This actin monomer becomes the first monomer of the new daughter filament. This paper provides the biochemical and biophysical basis for actin filament formation, necessary for cell shape and motility
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影响因子：
21.3
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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通讯作者：
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DOI：
10.1073/pnas.261419298
发表时间：
2001-12-18
影响因子：
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作者：
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通讯作者：
Mullins, RD