Structural basis of actin sequestration by thymosin-β4:: implications for WH2 proteins
Structural basis of actin sequestration by thymosin-β4:: implications for WH2 proteins
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DOI：
10.1038/sj.emboj.7600372
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发表时间：
2004-09-15
期刊：
影响因子：
11.4
通讯作者：
Robinson, RC
中科院分区：
文献类型：
--
作者：
Irobi, E;Aguda, AH;Robinson, RC
WH2(Wiscott-Aldridge综合征蛋白同源结构域2)重复序列是一种肌动蛋白相互作用的基序，存在于单体隔离和细丝组装蛋白中。我们通过在明胶蛋白结构域1和Tbeta4的C-末端一半(G1-Tbeta4)之间建立了杂交，稳定了典型的WH2家族成员胸腺素-Beta4(Tbeta4)相对于肌动蛋白的作用。这种混合蛋白隔离肌动蛋白单体，切断肌动蛋白细丝，充当一个漏水的带刺端帽。在这里，我们给出了G1-Tbeta4：肌动蛋白复合体在2埃分辨率下的结构。结构表明，Tbeta4通过覆盖肌动蛋白单体的两端来隔离，并且TB4和Profilin之间的肌动蛋白交换是通过结合位点的微小重叠来调节的。该结构意味着多个包含WH2基序的蛋白质将与肌动蛋白细丝纵向结合。最后，我们讨论了WH2基序在Arp2/3激活中的作用。
The WH2 (Wiscott - Aldridge syndrome protein homology domain 2) repeat is an actin interacting motif found in monomer sequestering and filament assembly proteins. We have stabilized the prototypical WH2 family member, thymosin-beta4 (Tbeta4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tbeta4 (G1-Tbeta4). This hybrid protein sequesters actin monomers, severs actin filaments and acts as a leaky barbed end cap. Here, we present the structure of the G1-Tbeta4: actin complex at 2Angstrom resolution. The structure reveals that Tbeta4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tb4 and profilin is mediated by a minor overlap in binding sites. The structure implies that multiple WH2 motif-containing proteins will associate longitudinally with actin filaments. Finally, we discuss the role of the WH2 motif in arp2/3 activation.