胸腺素β4对肌动蛋白的隔离作用的结构基础：对WH2蛋白的启示
Structural basis of actin sequestration by thymosin-beta4: implications for WH2 proteins.
作者信息
Irobi Edward, Aguda Adeleke H, Larsson Mårten, Guerin Christophe, Yin Helen L, Burtnick Leslie D, Blanchoin Laurent, Robinson Robert C
机构信息
Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden.
出版信息
EMBO J. 2004 Sep 15;23(18):3599-608. doi: 10.1038/sj.emboj.7600372. Epub 2004 Aug 26.
Abstract
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 2 A resolution. The structure reveals that Tbeta4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tbeta4 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.
摘要
WH2（威斯科特-奥尔德里奇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基序，存在于单体隔离蛋白和细丝组装蛋白中。我们通过在凝溶胶蛋白结构域1和胸腺素β4（Tβ4）的C端一半之间创建一个杂交体（G1-Tβ4），使典型的WH2家族成员胸腺素β4相对于肌动蛋白更加稳定。这种杂交蛋白隔离肌动蛋白单体，切断肌动蛋白细丝，并作为一个有泄漏的肌动蛋白丝正极帽发挥作用。在此，我们展示了分辨率为2埃的G1-Tβ4：肌动蛋白复合物的结构。该结构显示，Tβ4通过封闭肌动蛋白单体的两端来进行隔离，并且Tβ4和profilin之间肌动蛋白的交换是由结合位点的微小重叠介导的。该结构表明，多种含WH2基序的蛋白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。
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