Program in Cell and Molecular Biology, Institute of Biotechnology, University of Helsinki, Finland.
Cytoskeleton (Hoboken). 2011 Sep;68(9):471-90. doi: 10.1002/cm.20530. Epub 2011 Sep 13.
Actin filaments form contractile and protrusive structures that play central roles in many processes such as cell migration, morphogenesis, endocytosis, and cytokinesis. During these processes, the dynamics of the actin filaments are precisely regulated by a large array of actin-binding proteins. The actin-depolymerizing factor homology (ADF-H) domain is a structurally conserved protein motif, which promotes cytoskeletal dynamics by interacting with monomeric and/or filamentous actin, and with the Arp2/3 complex. Despite their structural homology, the five classes of ADF-H domain proteins display distinct biochemical activities and cellular roles, only parts of which are currently understood. ADF/cofilin promotes disassembly of aged actin filaments, whereas twinfilin inhibits actin filament assembly via sequestering actin monomers and interacting with filament barbed ends. GMF does not interact with actin, but instead binds Arp2/3 complex and promotes dissociation of Arp2/3-mediated filament branches. Abp1 and drebrin are multidomain proteins that interact with actin filaments and regulate the activities of other proteins during various actin-dependent processes. The exact function of coactosin is currently incompletely understood. In this review article, we discuss the biochemical functions, cellular roles, and regulation of the five groups of ADF-H domain proteins.
肌动蛋白丝形成收缩和突出结构，在细胞迁移、形态发生、胞吞作用和胞质分裂等许多过程中发挥核心作用。在这些过程中，肌动蛋白丝的动力学通过大量的肌动蛋白结合蛋白精确调节。肌动蛋白解聚因子同源（ADF-H）结构域是一种结构保守的蛋白质模体，通过与单体和/或丝状肌动蛋白以及 Arp2/3 复合物相互作用，促进细胞骨架动力学。尽管它们具有结构同源性，但五类 ADF-H 结构域蛋白表现出不同的生化活性和细胞作用，其中只有部分目前被理解。ADF/伴肌动蛋白促进老化肌动蛋白丝的解聚，而双丝氨酸抑制肌动蛋白丝组装，通过隔离肌动蛋白单体并与丝状末端相互作用。GMF 不与肌动蛋白相互作用，但与 Arp2/3 复合物结合并促进 Arp2/3 介导的丝分支解离。Abp1 和 drebrin 是与肌动蛋白丝相互作用并在各种依赖肌动蛋白的过程中调节其他蛋白质活性的多结构域蛋白。coactosin 的确切功能目前尚不完全清楚。在这篇综述文章中，我们讨论了五类 ADF-H 结构域蛋白的生化功能、细胞作用和调节。
