Arp2/3 复合物通过两个 WASP 蛋白结合和激活。
Arp2/3 complex is bound and activated by two WASP proteins.
机构信息
Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
出版信息
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):E472-9. doi: 10.1073/pnas.1100236108. Epub 2011 Jun 15.
Abstract
Actin related protein 2/actin related protein 3 (Arp2/3) complex nucleates new actin filaments in eukaryotic cells in response to signals from proteins in the Wiskott-Aldrich syndrome protein (WASP) family. The conserved VCA domain of WASP proteins activates Arp2/3 complex by inducing conformational changes and delivering the first actin monomer of the daughter filament. Previous models of activation have invoked a single VCA acting at a single site on Arp2/3 complex. Here we show that activation most likely involves engagement of two distinct sites on Arp2/3 complex by two VCA molecules, each delivering an actin monomer. One site is on Arp3 and the second is on ARPC1 and Arp2. The VCAs at these sites have distinct roles in activation. Our findings reconcile apparently conflicting literature on VCA activation of Arp2/3 complex and lead to a new model for this process.
摘要
肌动蛋白相关蛋白 2/3（Arp2/3）复合物在真核细胞中响应 Wiskott-Aldrich 综合征蛋白（WASP）家族蛋白的信号，引发新的肌动蛋白丝的形成。WASP 蛋白的保守 VCA 结构域通过诱导构象变化并输送子丝的第一个肌动蛋白单体来激活 Arp2/3 复合物。先前的激活模型推测单个 VCA 结构域在 Arp2/3 复合物的单个位点上起作用。在这里，我们表明激活很可能涉及两个不同的 VCA 分子与 Arp2/3 复合物上的两个不同位点结合，每个分子都输送一个肌动蛋白单体。一个位点在 Arp3 上，第二个位点在 ARPC1 和 Arp2 上。这些位点上的 VCAs 在激活中具有不同的作用。我们的发现调和了关于 VCA 激活 Arp2/3 复合物的文献中明显矛盾的观点，并为这一过程提出了一个新的模型。
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2
Determination of protein complex stoichiometry through multisignal sedimentation velocity experiments.通过多信号沉降速度实验测定蛋白质复合物的计量比。
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3
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4
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5
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6
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7
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8
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9
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10
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