Crystal structure of the actin binding domain of the cyclase-associated protein
Crystal structure of the actin binding domain of the cyclase-associated protein
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DOI：
10.1021/bi049071r
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发表时间：
2004-08-24
期刊：
影响因子：
2.9
通讯作者：
Almo, SC
中科院分区：
文献类型：
--
作者：
Dodatko, T;Fedorov, AA;Almo, SC
环化酶相关蛋白（CAP 或 Srv2p）是一种模块化肌动蛋白单体结合蛋白，可直接调节丝动力学，并参与许多复杂的发育和形态学过程，包括 mRNA 定位和细胞极性的建立。 C 端二聚化和肌动蛋白单体结合域 (C-CAP) 的晶体结构揭示了一种非常不寻常的二聚体，由具有六个右侧 β 螺旋卷曲、两侧为反平行 β 链的单体组成。结构域交换涉及每个单体的最后两条链，导致形成具有广泛界面的延伸二聚体。这种结构和生化特征为将动态肌动蛋白过程整合到细胞整体生理学中的多蛋白组装体的组织和潜在机械特性提供了新的见解。一个意想不到的发现是，C-CAP单体独特的三级结构为多种分子提供了结构模型，包括RP2和辅因子C、分别参与X连锁色素性视网膜炎和微管蛋白成熟的蛋白质，以及几种表现出非常多样化的结构域组织的未表征的蛋白质。因此，C-CAP 中存在的不寻常的右手 β 螺旋折叠似乎支持广泛的生物学功能。
Cyclase-associated protein (CAP or Srv2p) is a modular actin monomer binding protein that directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity. The crystal structure of the C-terminal dimerization and actin monomer binding domain (C-CAP) reveals a highly unusual dimer, composed of monomers possessing six coils of right-handed beta-helix flanked by antiparallel beta-strands. Domain swapping, involving the last two strands of each monomer, results in the formation of an extended dimer with an extensive interface. This structural and biochemical characterization provides new insights into the organization and potential mechanistic properties of the multiprotein assemblies that integrate dynamic actin processes into the overall physiology of the cell. An unanticipated finding is that the unique tertiary structure of the C-CAP monomer provides a structural model for a wide range of molecules, including RP2 and cofactor C, proteins involved in X-linked retinitis pigmentosa and tubulin maturation, respectively, as well as several uncharacterized proteins that exhibit very diverse domain organizations. Thus, the unusual right-handed beta-helical fold present in C-CAP appears to support a wide range of biological functions.