Tropomodulins and tropomyosins: working as a team.
Tropomodulins and tropomyosins: working as a team.
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DOI：
10.1007/s10974-013-9349-6
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发表时间：
2013-08
影响因子：
2.7
通讯作者：
Kostyukova AS
中科院分区：
文献类型：
--
作者：
Colpan M;Moroz NA;Kostyukova AS
肌动蛋白丝是真核细胞中细胞骨架的主要组成部分，并参与重要的细胞功能，如细胞运动和肌肉收缩。原肌球蛋白是一种α-螺旋卷曲蛋白，覆盖肌动蛋白丝的凹槽并使其稳定。肌动蛋白丝长度通过原调节蛋白优化，其覆盖细丝的缓慢生长（尖端）以抑制聚合或解聚。原调节蛋白由两个结构不同的区域组成：N-末端和C-末端结构域。N端结构域含有两个原肌球蛋白结合位点和一个原肌球蛋白依赖性肌动蛋白结合位点，而C端结构域含有一个原肌球蛋白独立性肌动蛋白结合位点。在加帽过程中，原肌调节蛋白与两个原肌球蛋白分子和至少一个肌动蛋白分子结合。原调节蛋白与原肌球蛋白的相互作用是肌动蛋白丝组织的关键调节因子。原调节蛋白与原肌球蛋白的结合效力是异构体依赖性的。原调节蛋白/原肌球蛋白结合的亲和力影响原调节蛋白在细胞中肌动蛋白丝尖端的适当定位和加帽效率。原肌调节蛋白和原肌球蛋白是肌动蛋白丝网络的重要组成部分，使它们的存在在活细胞中不可或缺。在这里，我们描述了如何在原肌球蛋白结合位点的原调节蛋白的序列的一个小的差异可能会导致在肌细胞或非肌细胞的形态Tmod的本地化的巨大变化。我们还提出了最有前途的方向，研究和阐明的作用Tmod-TM相互作用的形成和维持的肌节和细胞骨架结构。
Actin filaments are major components of the cytoskeleton in eukaryotic cells and are involved in vital cellular functions such as cell motility and muscle contraction. Tropomyosin is an alpha-helical, coiled coil protein that covers the grooves of actin filaments and stabilizes them. Actin filament length is optimized by tropomodulin, which caps the slow growing (pointed end) of thin filaments to inhibit polymerization or depolymerization. Tropomodulin consists of two structurally distinct regions: the N-terminal and the C-terminal domains. The N-terminal domain contains two tropomyosin-binding sites and one tropomyosin-dependent actin-binding site, whereas the C-terminal domain contains a tropomyosin-independent actin-binding site. Tropomodulin binds to two tropomyosin molecules and at least one actin molecule during capping. The interaction of tropomodulin with tropomyosin is a key regulatory factor for actin filament organization. The binding efficacy of tropomodulin to tropomyosin is isoform-dependent. The affinities of tropomodulin/tropomyosin binding influence the proper localization and capping efficiency of tropomodulin at the pointed end of actin filaments in cells. Tropomodulin and tropomyosin are crucial constituents of the actin filament network, making their presence indispensable in living cells. Here we describe how a small difference in the sequence of the tropomyosin-binding sites of tropomodulin may result in dramatic change in localization of Tmod in muscle cells or morphology of non-muscle cells. We also suggest most promising directions to study and elucidate the role of Tmod-TM interaction in formation and maintenance of sarcomeric and cytoskeletal structure.