An atomic model of actin filaments cross-linked by fimbrin and its implications for bundle assembly and function.
An atomic model of actin filaments cross-linked by fimbrin and its implications for bundle assembly and function.
复制标题
肌动蛋白丝的原子模型，与fimbrin交联及其对束组件和功能的影响。
DOI：
10.1083/jcb.153.5.947
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发表时间：
2001-05-28
影响因子：
7.8
通讯作者：
Hanein, D
中科院分区：
文献类型：
--
作者：
Volkmann, N;DeRosier, D;Matsudaira, P;Hanein, D
肌动蛋白束对细胞的形状、分裂、粘附、运动和信号传导具有深远的影响。Fimmunoglobulin属于肌动蛋白捆绑蛋白的一个大家族，并且参与刷状缘微绒毛和内耳毛细胞的静纤毛中紧密有序的交联束的形成。这些三维（3D）束的多态性阻止了深入了解其形态发生和功能所需的详细结构表征。在这里，我们描述了与人类T-fimmatis交联的肌动蛋白的二维阵列的结构表征。通过电子显微镜、X射线晶体学和同源性建模获得的结构信息使我们能够建立第一个完整的肌动蛋白-fiminoblasts交联的分子模型。将阵列限制为二维使我们能够推断组分之间的空间关系、最终交联的模式以及交联内的柔性。结合骨架交联的原子模型、从阵列中推导出的交联规则以及肌动蛋白束原位的六角堆积，生成三维肌动蛋白骨架束的原子模型。此外，装配的肌动蛋白-fimbranes阵列表明肌动蛋白聚合，fimbranes结合，和crossbridge形成之间的耦合，大概是通过构象变化和亲和力变化之间的反馈实现的。
Actin bundles have profound effects on cellular shape, division, adhesion, motility, and signaling. Fimbrin belongs to a large family of actin-bundling proteins and is involved in the formation of tightly ordered cross-linked bundles in the brush border microvilli and in the stereocilia of inner ear hair cells. Polymorphism in these three-dimensional (3D) bundles has prevented the detailed structural characterization required for in-depth understanding of their morphogenesis and function. Here, we describe the structural characterization of two-dimensional arrays of actin cross-linked with human T-fimbrin. Structural information obtained by electron microscopy, x-ray crystallography, and homology modeling allowed us to build the first molecular model for the complete actin–fimbrin cross-link. The restriction of the arrays to two dimensions allowed us to deduce the spatial relationship between the components, the mode of fimbrin cross-linking, and the flexibility within the cross-link. The atomic model of the fimbrin cross-link, the cross-linking rules deduced from the arrays, and the hexagonal packing of actin bundles in situ were all combined to generate an atomic model for 3D actin–fimbrin bundles. Furthermore, the assembly of the actin–fimbrin arrays suggests coupling between actin polymerization, fimbrin binding, and crossbridge formation, presumably achieved by a feedback between conformational changes and changes in affinity.