研究揭示可溶性N

近日，华中科技大学Cong Ma及其课题组通过固态核磁，揭示了脂双层中可溶性N-乙酰亚胺敏感因子连接的蛋白质受体复合物组装结构机制。这一研究成果发表在2023年5月9日出版的国际学术期刊《美国化学会杂志》上。

在这项研究中，研究团队通过双极和标量固态NMR在脂双分子层中对Syb-2构象的不同装配状态进行了性质表征。他们的光谱分析显示了具有较多α螺旋的Syb-2 TMD的高度动态特性。化学位移扰动和突变分析表明，Syb-2和Syx-1 TMD之间的耦合是由Syb-2的Gly-100残基和Syb-2 TMD高流动性的C端部分一起介导的，也是内膜合并所必需。

他们的研究结果为Syb-2 TMD在推动膜融合的角色提供了新的见解，增加了当前对SNARE复合物装配的结构机制的理解。这项研究突出了在阐释膜蛋白机制的过程中膜环境的意义。

研究人员表示，突触囊泡融合是由可溶性N-乙酰亚胺敏感因子连接的蛋白质受体（SNARE）蛋白质，包括synaptobrevin-2 (Syb-2)、syntaxin-1 (Syx-1)和SNAP-25介导的。然而，包含大量接触的α螺旋从SNARE结构域到膜结合结构域（TMD）之间形成，是否对SNARE介导的膜融合是必要的仍然存在争议。

附：英文原文

Title: Structural Mechanism of Soluble N-ethylmaleimide-Sensitive Factor Attachment Protein Receptor Complex Assembly in Lipid Bilayers Revealed by Solid-State NMR

Author: Yan Zhang, Yaru Hu, Huayong Xie, Maili Liu, Jun Yang, Cong Ma

Issue&Volume: May 9, 2023

Abstract: Synaptic vesicle fusion is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, including synaptobrevin-2 (Syb-2),  syntaxin-1 (Syx-1), and SNAP-25. However, it remains controversial whether the formation of thoroughly contacted α-helical bundle from the SNARE motifs to the end of the transmembrane domains (TMDs) is necessary for SNARE-mediated membrane fusion. In this study, we characterized the conformation of Syb-2 in different assembly states using a combination of dipolar- and scalar-based solid-state NMR experiments in lipid bilayers. Our spectral analysis revealed a highly dynamic nature of the Syb-2 TMD with considerable α-helical contents. Chemical shift perturbation and mutational analysis indicated that the coupling between Syb-2 and Syx-1 TMDs mediated by residue Gly-100 of Syb-2 together with high mobility of the C-terminal segment of Syb-2 TMD are required for inner membrane merger. Our results provide new insights into the role of the Syb-2 TMD in driving membrane fusion, which improves the current understanding of the structural mechanism of SNARE complex assembly. This study highlights the significance of membrane environments in elucidating the mechanism of membrane proteins.

DOI: 10.1021/jacs.3c00764

Source: https://pubs.acs.org/doi/10.1021/jacs.3c00764

JACS：《美国化学会志》，创刊于1879年。隶属于美国化学会，最新IF：16.383 官方网址：https://pubs.acs.org/journal/jacsat 投稿链接：https://acsparagonplus.acs.org/psweb/loginForm?code=1000