德国马克斯普朗克分子生理学研究所Stefan Raunser团队的论文通过解析完整肌原纤维的结构，揭示了星云蛋白调节细丝纤维的机制。该项研究成果发表在2022年2月18日出版的《科学》上。

研究人员使用低温电子断层扫描和亚断层图像相结合的方法揭示了与完整肌节内细丝结合的天然星云蛋白结构。这种原位重建提供了星云蛋白和肌动蛋白之间相互作用的高分辨率细节，证明了星云蛋白的稳定作用。与细丝结合的肌球蛋白表现出不同的颈部结构，突出了其在肌肉中固有的结构变异性。

出乎意料的是，星云蛋白并没有直接与肌球蛋白或原肌球蛋白相互作用，而是通过星云蛋白上两个潜在结合基序与肌钙蛋白T接头相互作用，这解释了其调节作用。 该结构表明星云蛋白可作为细丝的“分子尺”，并为研究线虫肌病提供了分子基础。

研究人员表示，在骨骼肌中，星云蛋白很稳定并调节细丝长度，但其潜在的机制仍然不清。

附：英文原文

Title: Structures from intact myofibrils reveal mechanism of thin filament regulation through nebulin

Author: Zhexin Wang, Michael Grange, Sabrina Pospich, Thorsten Wagner, Ay Lin Kho, Mathias Gautel, Stefan Raunser

Issue&Volume: 2022-02-18

Abstract: In skeletal muscle, nebulin stabilizes and regulates the length of thin filaments, but the underlying mechanism remains nebulous. In this work, we used cryo–electron tomography and subtomogram averaging to reveal structures of native nebulin bound to thin filaments within intact sarcomeres. This in situ reconstruction provided high-resolution details of the interaction between nebulin and actin, demonstrating the stabilizing role of nebulin. Myosin bound to the thin filaments exhibited different conformations of the neck domain, highlighting its inherent structural variability in muscle. Unexpectedly, nebulin did not interact with myosin or tropomyosin, but it did interact with a troponin T linker through two potential binding motifs on nebulin, explaining its regulatory role. Our structures support the role of nebulin as a thin filament “molecular ruler” and provide a molecular basis for studying nemaline myopathies.

DOI: abn1934

Source: https://www.science.org/doi/10.1126/science.abn1934