Dominguez Roberto
Department of Physiology, University of Pennsylvania School of Medicine, 3700 Hamilton Walk, Philadelphia, PA 19104, USA.
Ann N Y Acad Sci. 2007 Sep;1112:86-94. doi: 10.1196/annals.1415.011. Epub 2007 Apr 27.
Remodeling of the actin cytoskeleton in cells is tightly regulated by a vast number of actin-binding proteins (ABPs). These proteins interact with actin via a limited set of conserved folding motifs. One of the most abundant actin-binding motifs is the beta-thymosin fold, represented by the prototypical actin-monomer sequestering protein thymosin-beta4. Among many cytoskeletal proteins, the beta-thymosin fold adopts a shorter form, known as the WASP homology domain 2. Some characteristic features of the beta-thymosin/WH2 fold include its small size (17-43 aa), significant sequence and length variability, frequent occurrence in the form of tandem repeats, and remarkable multifunctionality. This paper discusses the relationship between structure and function of the beta-thymosin/WH2 fold on the basis of four examples: (1) actin monomer sequestration (thymosin-beta4), (2) actin filament nucleation (WASP-Arp2/3 complex, Lmod, and spire), (3) actin filament elongation (Ena/VASP), and (4) cytoskeleton scaffolding (IRSp53 and MIM). Although the core function of the beta-thymosin/WH2 domain in all these proteins is actin binding, specific changes in the sequence of the domain and modular organization of the proteins in which it is found give rise to diverse functions in the regulation of actin cytoskeleton dynamics.
细胞中肌动蛋白细胞骨架的重塑受到大量肌动蛋白结合蛋白（ABP）的严格调控。这些蛋白通过一组有限的保守折叠基序与肌动蛋白相互作用。最丰富的肌动蛋白结合基序之一是β-胸腺素折叠，由典型的肌动蛋白单体隔离蛋白胸腺素-β4代表。在许多细胞骨架蛋白中，β-胸腺素折叠采用较短的形式，称为WASP同源结构域2。β-胸腺素/WH2折叠的一些特征包括其小尺寸（17 - 43个氨基酸）、显著的序列和长度变异性、以串联重复形式频繁出现以及显著的多功能性。本文基于四个例子讨论β-胸腺素/WH2折叠的结构与功能之间的关系：（1）肌动蛋白单体隔离（胸腺素-β4），（2）肌动蛋白丝成核（WASP - Arp2/3复合物、Lmod和Spire），（3）肌动蛋白丝延伸（Ena/VASP），以及（4）细胞骨架支架（IRSp53和MIM）。尽管所有这些蛋白中β-胸腺素/WH2结构域的核心功能是肌动蛋白结合，但该结构域序列的特定变化以及其所在蛋白的模块化组织在肌动蛋白细胞骨架动力学调控中产生了多种功能。
