中国科学院武汉物理与数学研究所杨俊团队,报道了天然细胞膜通过增强其跨膜螺旋的缓慢集体运动,促进MscL的通道活性
大电导机械敏感通道蛋白(MscL)是细胞对膜张力的机械电阀。膜环境对MscL通道活性的影响及其潜在机制尚不清楚。
该文中,研究人员开发了一种新的样品制备方案,可以检测细胞膜中MscL的高质量1H检测固态NMR光谱,从而能够对其动力学进行位点特异性分析。测量了合成和天然膜中51个MscL残基的偶极序参数和自旋弛豫速率。
动力学数据显示,虽然MscL在两种膜环境中保持相似的刚性,但它在天然细胞膜中表现出增强的缓慢集体运动。分子动力学模拟表明,慢运动通过促进蛋白质-膜相互作用,在MscL的机械敏感性中起着关键作用。
该研究考察了细胞膜中膜蛋白的原子分辨率动力学,并为膜蛋白动力学的功能意义提供了新的见解。
附:英文原文
Title: Native Cellular Membranes Facilitate Channel Activity of MscL by Enhancing Slow Collective Motions of Its Transmembrane Helices
Author: Huan Tan, Weijing Zhao, Mojie Duan, Yongxiang Zhao, Yan Zhang, Huayong Xie, Qiong Tong, Jun Yang
Issue&Volume: November 6, 2024
Abstract: Mechanosensitive channels of large conductance (MscL) serve as a mechanoelectrical valve of cells in response to the membrane tension. The influence of membrane environments on the MscL channel activity and the underlying mechanism remains unclear. Herein, we developed a new sample preparation protocol that allows for the detection of high-quality 1H-detected solid-state NMR spectra of MscL in cellular membranes, enabling site-specific analysis of its dynamics. Dipolar order parameters and spin relaxation rates are measured for 51 residues of MscL in synthetic and native membranes. The dynamics data reveal that while MscL maintains a similar rigidity in both membrane environments, it exhibits enhanced slow collective motions in the native cellular membranes. Molecular dynamics simulations demonstrate the critical role of slow motions in the mechanosensitivity of MscL by promoting protein–membrane interactions. This study examines atomic-resolution dynamics of a membrane–protein in cellular membranes and provides novel insights into the functional significance of membrane–protein dynamics.
DOI: 10.1021/jacs.4c07779
Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c07779
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