The bacterial ESCRT-III PspA rods thin lipid tubules and increase membrane curvature through helix α0 interactions

• 成果类型: Article
• 署名作者: Hudina, Esther; Schott-Verdugo, Stephan; Junglas, Benedikt; Kutzner, Mirka; Ritter, Ilona; Hellmann, Nadja; Schneider, Dirk; Gohlke, Holger; Sachse, Carsten
• 署名单位: Helmholtz Association; Research Center Julich; Heinrich Heine University Dusseldorf; Helmholtz Association; Research Center Julich; Johannes Gutenberg University of Mainz; Johannes Gutenberg University of Mainz; Heinrich Heine University Dusseldorf
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13777
• DOI: 10.1073/pnas.2506286122
• 发表日期: 2025-08-12
• 关键词: phage-shock-protein; molecular-dynamics; escherichia-coli; cryo-em; amphipathic helices; a pspa; vipp1; identification; deformation; inhibition

摘要

The phage shock protein A (PspA), a bacterial member of the endosomal sorting complexes required for transport (ESCRT)-III superfamily, forms rod-shaped helical assemblies that internalize membrane tubules. The N-terminal helix alpha 0 of PspA (and other ESCRT-III members) has been suggested to act as a membrane anchor; the detailed mechanism, however, of how it binds to membranes and eventually triggers membrane fusion and/or fission events remains unclear. By solving a total of 15 cryoelectron microscopy (cryo-EM) structures of PspA and a truncation lacking the N-terminal helix alpha 0 in the presence of Escherichia coli polar lipid membranes, we show in molecular detail how PspA interacts with and remodels membranes: Binding of the N-terminal helix alpha 0 in the outer tubular membrane leaflet induces membrane curvature, supporting membrane tubulation by PspA. Detailed molecular dynamics simulations and free energy computations of interactions between the helix alpha 0 and negatively charged membranes suggest a compensating mechanism between helix-membrane interactions and the energy contributions required for membrane bending. The energetic considerations are in line with the membrane structures observed in the cryo-EM images of tubulated membrane vesicles, fragmented vesicles inside tapered PspA rods, and shedded vesicles emerging at the thinner PspA rod ends. Our results provide insights into the molecular determinants and a potential mechanism of vesicular membrane remodeling mediated by a member of the ESCRT-III superfamily.