Cryo- EM structure of the prohibitin complex in open conformation

• 成果类型: Article
• 署名作者: Hong, Sixing; Guan, Zeyuan; Zhang, Liying; Zhuang, Jinjin; Yan, Ling; Liu, Yanjun; Liu, Zhu; Wang, Qiang; Yin, Ping
• 署名单位: Huazhong Agricultural University; Hubei Hongshan Laboratory
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2512430122
• 发表日期: 2025-09-23
• 页码: e2512430122
• 关键词: prohibitin complex; mitochondria; scaffold; membrane microdomain; cryo-em; mitochondrial; survival; cardiolipin; proteins; roles

摘要

Prohibitin 1 (PHB1) and Prohibitin 2 (PHB2), two conserved prohibitin members, are primarily localized to the mitochondrial inner membrane (MIM) to form a nanoscale macromolecular prohibitin complex. This prohibitin complex can facilitate the spatial organization of proteins and lipids, thus maintaining cellular metabolism and homeostasis, but its architecture remains largely unknown. Here, we report the cryo- EM structure of a prohibitin complex at 2.8 & Aring; resolution, which contains 11 PHB1-PHB2 heterodimers. This complex displays a bell- like cage, consisting of a lid and a wall, which creates an intermembrane space- facing compartment for the MIM. The lid of the cage is stably assembled, and it is responsible for the prohibitin complex formation. In contrast, the wall of the cage is flexible and exhibits lateral openings, providing a channel for intramembrane exchange of proteins and lipids. These findings provide a structural basis for understanding the scaffold role of the prohibitin complex in organizing intramembrane proteins and lipids.