Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain
Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain
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DOI：
10.1038/nature03251
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发表时间：
2005-02-03
期刊：
影响因子：
64.8
通讯作者：
Rosen, MK
中科院分区：
文献类型：
--
作者：
Otomo, T;Tomchick, DR;Rosen, MK
保守的成蛋白同源2（FH2）结构域使肌动蛋白丝成核，并保持与生长丝的带刺端结合。在此我们报道了酵母Bni1p FH2结构域与四甲基罗丹明 - 肌动蛋白复合物的晶体结构。FH2二聚体中的两个结构单元各自以类似于肌动蛋白丝中的取向结合两个肌动蛋白，这表明该结构可作为丝核发挥作用。异二聚体FH2突变体的生化特性表明，野生型蛋白在带刺端的两种结合状态之间平衡：一种允许单体结合，另一种允许单体解离。这些状态之间的相互转换使得在结合的FH2结构域存在的情况下，带刺端能够进行连续性的聚合和解聚。构象和结合平衡在动力学和/或热力学上的差异可以解释不同FH2结构域的可变活性以及肌动蛋白结合蛋白前纤维蛋白对FH2功能的影响。
The conserved formin homology 2 (FH2) domain nucleates actin filaments and remains bound to the barbed end of the growing filament. Here we report the crystal structure of the yeast Bni1p FH2 domain in complex with tetramethylrhodamine - actin. Each of the two structural units in the FH2 dimer binds two actins in an orientation similar to that in an actin filament, suggesting that this structure could function as a filament nucleus. Biochemical properties of heterodimeric FH2 mutants suggest that the wild-type protein equilibrates between two bound states at the barbed end: one permitting monomer binding and the other permitting monomer dissociation. Interconversion between these states allows processive barbed-end polymerization and depolymerization in the presence of bound FH2 domain. Kinetic and/or thermodynamic differences in the conformational and binding equilibria can explain the variable activity of different FH2 domains as well as the effects of the actin-binding protein profilin on FH2 function.