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心脏细肌丝的冷冻电镜结构揭示了肌钙蛋白的 3D 结构。

Cryo-EM structures of cardiac thin filaments reveal the 3D architecture of troponin.

机构信息

Department of Anatomy and Structural Biology, Graduate School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.

Department of Cell Biology and Anatomy, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

出版信息

J Struct Biol. 2020 Mar 1;209(3):107450. doi: 10.1016/j.jsb.2020.107450. Epub 2020 Jan 16.

Abstract

Troponin is an essential component of striated muscle and it regulates the sliding of actomyosin system in a calcium-dependent manner. Despite its importance, the structure of troponin has been elusive due to its high structural heterogeneity. In this study, we analyzed the 3D structures of murine cardiac thin filaments using a cryo-electron microscope equipped with a Volta phase plate (VPP). Contrast enhancement by a VPP enabled us to reconstruct the entire repeat of the thin filament. We determined the orientation of troponin relative to F-actin and tropomyosin, and characterized the interactions between troponin and tropomyosin. This study provides a structural basis for understanding the molecular mechanism of actomyosin system.

摘要

肌钙蛋白是横纹肌的重要组成部分,它以钙离子依赖的方式调节肌动球蛋白系统的滑动。尽管肌钙蛋白很重要,但由于其高度结构异质性,其结构一直难以捉摸。在这项研究中,我们使用配备有 Volta 相板 (VPP) 的冷冻电子显微镜分析了鼠心脏细肌丝的 3D 结构。VPP 的对比度增强使我们能够重建细肌丝的整个重复序列。我们确定了肌钙蛋白相对于 F-肌动蛋白和原肌球蛋白的方向,并表征了肌钙蛋白和原肌球蛋白之间的相互作用。这项研究为理解肌球蛋白系统的分子机制提供了结构基础。

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