期刊论文

Rui Wang<&wdkj&>Ying-Zhe Fan<&wdkj&>Ye Yu

英文

科学通报(英文版)

2095-9273

2022

67

10

1062-1076

10.1016/j.scib.2022.02.016

This work was supported by the Natural Science Foundation of Jiangsu Province (BK20202002), the National Natural Science Foundation of China (81603409, 31900808, 81902480, 21977021, 31570832, 31971146, and 31971042), Innovation and Entrepreneurship Talent Program of Jiangsu Province, State Key Laboratory of Utilization of Woody Oil Resource (2019XK2002), the Natural Science Foundation of Hunan Province (2018JJ1012), Hunan “Huxiang” High-level Talent Program (2021), and “Xing Yao” Leading Scholars of China Pharmaceutical University (2021). Ye Yu designed the project; Meng-Yang Sun, Yang Yang, Xue Zhang, and Wen-Wen Cui performed cell culture, patch-clamp recording, Western blotting, and VCF; Ying-Zhe Fan, Peng-Cheng Yu, Di Liu, and Wen-Hui Wang did cell apoptosis analysis; Meng-Yang Sun, Xiao-Na Yang did mutations; Ye Yu, and Peng Cao did NMA and MD simulations; Ye Yu, Ying-Zhe Fan, Yun-Tao Lei, Chang-Zhu Li, and Xing-Hua Li analyzed data; Rui Wang supervised Meng-Yang Sun; and Ye Yu, Michael X. Zhu, and Heng Shan Wang wrote the manuscript. All authors discussed the results and commented on the manuscript.

本校为其他机构

Transient receptor potential vanilloid 1 (TRPV1) channel plays an important role in a wide range of physiological and pathological processes, and a comprehensive understanding of TRPV1 gating will create opportunities for therapeutic intervention. Recent incredible advances in cryo-electron microscopy (cryo-EM) have yielded high-resolution structures of all TRPV subtypes (TRPV1–6) and all of them share highly conserved six transmembrane (TM) domains (S1–S6). As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agon...

瞬时受体电位香草素1（TRPV1）通道参与了哺乳动物体内许多重要的生理和病理过程,对其门控机制的全面了解有助于为相关疾病的治疗干预提供可能.近年来冷冻电子显微镜（cryo-EM）技术在结构生物学中取得了惊人的成果,所有TRPV亚型（TRPV1±6）的高分辨率结构也得到了解析:它们都具有高度保守的6个跨膜（TM）结构域（S1±S6）,与电压门控离子通道（VGICs）相似.并且,在结合了香草素激动剂（辣椒素或树脂毒素）的TRPV1通道开放结构中, TM螺旋S1±S4形成一束,保持静止状态,这也证明了TRP和VGICs通道功能和门控机制的差异.然而,本研究认为S1±S4的动态变化而非静止是辣椒素激活TRPV1的必要条件.通过荧...