{"title":"Structural Basis for Efficient Fo Motor Rotation Revealed by MCMD simulation and Structural Analysis.","authors":"Shintaroh Kubo, Hiroyuki Noji","doi":"10.1016/j.bpj.2025.10.006","DOIUrl":null,"url":null,"abstract":"<p><p>F<sub>o</sub> domain of ATP synthase functions as a rotary molecular motor, coupling proton translocation with the rotation of the c-ring rotor. This process involves proton uptake at the entry half channel, rotor rotation, and proton release to the exit half channel. While the overall coupling mechanism is established, the design principle for efficient rotation remains unclear. Here, we employed hybrid molecular simulations-combining coarse-grained modeling and Monte Carlo methods-to investigate the roles of side chain flexibility at proton-binding residues and the angular mismatch between the proton uptake process and the proton release process. Our results indicate that both factors promote rotational activity, with side chain flexibility playing a more significant role. Comparable analysis of F<sub>o</sub> structures from different species revealed that the key residue geometry is conserved, and that the asymmetric geometry of the two half channels aligns with the mechanism suggested by simulation. These findings highlight a conserved design principle that enhances rotational efficiency and offer a mechanistic basis for engineering synthetic rotary systems.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biophysical journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.bpj.2025.10.006","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOPHYSICS","Score":null,"Total":0}
引用次数: 0
Abstract
Fo domain of ATP synthase functions as a rotary molecular motor, coupling proton translocation with the rotation of the c-ring rotor. This process involves proton uptake at the entry half channel, rotor rotation, and proton release to the exit half channel. While the overall coupling mechanism is established, the design principle for efficient rotation remains unclear. Here, we employed hybrid molecular simulations-combining coarse-grained modeling and Monte Carlo methods-to investigate the roles of side chain flexibility at proton-binding residues and the angular mismatch between the proton uptake process and the proton release process. Our results indicate that both factors promote rotational activity, with side chain flexibility playing a more significant role. Comparable analysis of Fo structures from different species revealed that the key residue geometry is conserved, and that the asymmetric geometry of the two half channels aligns with the mechanism suggested by simulation. These findings highlight a conserved design principle that enhances rotational efficiency and offer a mechanistic basis for engineering synthetic rotary systems.
期刊介绍:
BJ publishes original articles, letters, and perspectives on important problems in modern biophysics. The papers should be written so as to be of interest to a broad community of biophysicists. BJ welcomes experimental studies that employ quantitative physical approaches for the study of biological systems, including or spanning scales from molecule to whole organism. Experimental studies of a purely descriptive or phenomenological nature, with no theoretical or mechanistic underpinning, are not appropriate for publication in BJ. Theoretical studies should offer new insights into the understanding ofexperimental results or suggest new experimentally testable hypotheses. Articles reporting significant methodological or technological advances, which have potential to open new areas of biophysical investigation, are also suitable for publication in BJ. Papers describing improvements in accuracy or speed of existing methods or extra detail within methods described previously are not suitable for BJ.