德国马克斯·普朗克分子生理学研究所Stefan Raunser近期取得重要工作进展，他们研究发现了松弛心脏肌节中天然肌球蛋白丝的结构。相关研究成果2023年11月1日在线发表于《自然》杂志上。
据介绍，粗丝是肌节的关键组成部分，肌节是横纹肌的基本单位。 粗丝蛋白的改变与家族性肥厚性心肌病和其它心脏及肌肉疾病有关。 尽管粗丝具有核心重要性，但其分子结构仍不清楚。
研究人员展示了通过冷冻电子断层扫描确定的放松状态下天然心脏肌节的分子结构。 研究人员对粗丝的重建揭示了肌球蛋白、肌联蛋白和肌球蛋白结合蛋白 C (MyBP-C) 的三维组织。 肌球蛋白分子的排列取决于它们沿肌丝的位置，这表明其在应变敏感性和力产生方面具有特殊的能力。 三对肌联蛋白-α 和肌联蛋白-β 链沿着肌丝轴向延伸，与肌球蛋白尾部交织在一起，可能协调肌节的长度依赖性激活。 值得注意的是，三个肌动蛋白-α 链沿着粗丝的整个长度延伸，而肌动蛋白-β 链则不然。 该结构还表明，MyBP-C 桥接细丝和粗丝，其羧基末端区域与肌球蛋白尾部结合，并以不可预见的方式直接稳定肌球蛋白头部的关闭状态。
总之，这些结果为未来研究涉及肌节成分的肌肉疾病奠定了基础。
附：英文原文
Title: Structure of the native myosin filament in the relaxed cardiac sarcomere
Author: Tamborrini, Davide, Wang, Zhexin, Wagner, Thorsten, Tacke, Sebastian, Stabrin, Markus, Grange, Michael, Kho, Ay Lin, Rees, Martin, Bennett, Pauline, Gautel, Mathias, Raunser, Stefan
Issue&Volume: 2023-11-01
Abstract: The thick filament is a key component of sarcomeres, the basic units of striated muscle1. Alterations in thick filament proteins are associated with familial hypertrophic cardiomyopathy and other heart and muscle diseases2. Despite the central importance of the thick filament, its molecular organization remains unclear. Here we present the molecular architecture of native cardiac sarcomeres in the relaxed state, determined by cryo-electron tomography. Our reconstruction of the thick filament reveals the three-dimensional organization of myosin, titin and myosin-binding protein C (MyBP-C). The arrangement of myosin molecules is dependent on their position along the filament, suggesting specialized capacities in terms of strain susceptibility and force generation. Three pairs of titin-α and titin-β chains run axially along the filament, intertwining with myosin tails and probably orchestrating the length-dependent activation of the sarcomere. Notably, whereas the three titin-α chains run along the entire length of the thick filament, titin-β chains do not. The structure also demonstrates that MyBP-C bridges thin and thick filaments, with its carboxy-terminal region binding to the myosin tails and directly stabilizing the OFF state of the myosin heads in an unforeseen manner. These results provide a foundation for future research investigating muscle disorders involving sarcomeric components.
DOI: 10.1038/s41586-023-06690-5
Source: https://www.nature.com/articles/s41586-023-06690-5
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
