Nolen Brad J, Pollard Thomas D
Departments of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA.
J Biol Chem. 2008 Sep 26;283(39):26490-8. doi: 10.1074/jbc.M802607200. Epub 2008 Jul 18.
Arp2/3 (actin-related protein 2/3) complex is a seven-subunit complex that nucleates branched actin filaments in response to cellular signals. Nucleation-promoting factors such as WASp/Scar family proteins activate the complex by facilitating the activating conformational change and recruiting the first actin monomer for the daughter branch. Here we address the role of the Arp2 subunit in the function of Arp2/3 complex by isolating a version of the complex lacking Arp2 (Arp2Delta Arp2/3 complex) from fission yeast. An x-ray crystal structure of the DeltaArp2 Arp2/3 complex showed that the rest of the complex is unperturbed by the loss of Arp2. However, the Arp2Delta Arp2/3 complex was inactive in actin nucleation assays, indicating that Arp2 is essential to form a branch. A fluorescence anisotropy assay showed that Arp2 does not contribute to the affinity of the complex for Wsp1-VCA, a Schizosaccharomyces pombe nucleation-promoting factor protein. Fluorescence resonance energy transfer experiments showed that the loss of Arp2 does not prevent VCA from recruiting an actin monomer to the complex. Truncation of the N terminus of ARPC5, the smallest subunit in the complex, increased the yield of Arp2Delta Arp2/3 complex during purification but did not compromise nucleation activity of the full Arp2/3 complex.
Arp2/3(肌动蛋白相关蛋白2/3)复合体是一种七亚基复合体,可响应细胞信号使肌动蛋白丝成核形成分支。诸如WASp/Scar家族蛋白等成核促进因子通过促进激活构象变化并为子分支募集第一个肌动蛋白单体来激活该复合体。在这里,我们通过从裂殖酵母中分离出一种缺乏Arp2的复合体版本(Arp2缺失型Arp2/3复合体)来研究Arp2亚基在Arp2/3复合体功能中的作用。Arp2缺失型Arp2/3复合体的X射线晶体结构表明,该复合体的其余部分不受Arp2缺失的影响。然而,Arp2缺失型Arp2/3复合体在肌动蛋白成核试验中无活性,这表明Arp2对于形成分支至关重要。荧光各向异性试验表明,Arp2对该复合体与Wsp1-VCA(一种粟酒裂殖酵母成核促进因子蛋白)的亲和力没有贡献。荧光共振能量转移实验表明,Arp2的缺失并不妨碍VCA将肌动蛋白单体募集到复合体中。复合体中最小的亚基ARPC5的N端截短,在纯化过程中提高了Arp2缺失型Arp2/3复合体的产量,但并未损害完整Arp2/3复合体的成核活性。