STRUCTURE OF AN ACTIN CROSS LINKING DOMAIN FROM HUMAN FIMBRIN

肌动蛋白交联蛋白将丝状(F-)肌动蛋白组织成 更高阶的组件，例如捆绑和网络，它们是 对包括细胞运动在内的生物过程很重要， 胞质分裂和肿瘤发生。Fimbrin是具有代表性的成员之一 最大的肌动蛋白交联剂超家族，其特征是 由一个保守的275个氨基酸组成的F-肌动蛋白结合区。我们有 确定了N-末端肌动蛋白结合的晶体结构 人纤毛蛋白的结构域(ABD1)到2.4E分辨率，这代表 肌动蛋白-交联域的第一个高分辨结构。 ABD1晶体的初始表征是使用 布鲁克海文国家实验室的同步辐射，光束线X9B， 晶体的衍射率至少达到1.9E分辨率。ABD1是 一种尺寸为(60x40x40E3)的椭球分子，具有新的折叠 H由两个钙蛋白同源(CH)亚域组成。CH域可以 HServe靶向一系列蛋白质，包括信号蛋白， 到细胞骨架组件。在与David DeRosier的合作中，我们 他现在已经将这种x射线结构对接到28E电子中 A修饰的肌动蛋白细丝的显微结构重建 可比的Fimbrin的HFrameet。这项工作是第一次 提供了一个用于交联组装体的原子模型。

Actin crosslinking proteins organize filamentous (F-) actin into higher order assemblies such as bundles and networks which are important for biological processes including cell motility, cytokinesis and tumorigenesis. Fimbrin is a representative member of the largest superfamily of actin crosslinkers which is characterized by a conserved 275 amino acid F-actin binding domain. We have determined the crystal structure of the N-terminal actin binding domain of human fimbrin (ABD1) to 2.4 E resolution, which represents the first high resolution structure of an actin-crosslinking domain. Initial characterization of ABD1 crystals was performed using synchrotron radiation at Brookhaven National Laboratory, Beamline X9B, where the crystals diffracted to at least 1.9 E resolution. ABD1 is an ellipsoid molecule of dimensions (60x40x40E 3, and has a novel fold Hcomposed of two calponin homology (CH) subdomains. CH domains may Hserve to target a number of proteins, including signaling proteins, to Hcytoskeletal components. In collaboration with David DeRosier, we Hhave now docked this x-ray structure into the 28E electron microscopic Hreconstruction of actin filaments decorated with a comparable Hfragmenet of fimbrin. This work has for the first time provided an Hatomic model for the crosslinked assembly.