Tropomodulins are a family of important regulators of actin dynamics at the pointed ends of actin filaments. Four isoforms of tropomodulin, Tmod1‐Tmod4, are expressed in vertebrates. Binding of tropomodulin to the pointed end is dependent on tropomyosin, an actin binding protein that itself is represented in mammals by up to 40 isoforms. The understanding of the regulatory role of the tropomodulin/tropomyosin molecular diversity has been limited due to the lack of a three‐dimensional structure of the tropomodulin/tropomyosin complex. In this study, we mapped tropomyosin residues interacting with two tropomyosin‐binding sites of tropomodulin and generated a three‐dimensional model of the tropomodulin/tropomyosin complex for each of these sites. The models were refined by molecular dynamics simulations and validated via building a self‐consistent three‐dimensional model of tropomodulin assembly at the pointed end. The model of the pointed‐end Tmod assembly offers new insights in how Tmod binding ensures tight control over the pointed end dynamics.

中文翻译：

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肌动蛋白丝尖端原调节蛋白组装的结构见解


原调节蛋白是肌动蛋白丝尖端肌动蛋白动力学的重要调节剂家族。原调节蛋白的四种异构体 Tmod1-Tmod4 在脊椎动物中表达。原调节蛋白与尖端的结合依赖于原肌球蛋白，原肌球蛋白是一种肌动蛋白结合蛋白，其本身在哺乳动物中具有多达 40 种异构体。由于原调节蛋白/原肌球蛋白复合物缺乏三维结构，对原调节蛋白/原肌球蛋白分子多样性的调节作用的理解受到限制。在本研究中，我们绘制了与原调节蛋白的两个原肌球蛋白结合位点相互作用的原肌球蛋白残基，并为每个位点生成了原调节蛋白/原肌球蛋白复合物的三维模型。该模型通过分子动力学模拟进行了改进，并通过在尖端建立原调节蛋白组装的自洽三维模型进行了验证。尖端 Tmod 组件的模型为 Tmod 结合如何确保对尖端动力学的严格控制提供了新的见解。