{"title":"Theoretical insights into rotary mechanism of MotAB in the bacterial flagellar motor","authors":"Shintaroh Kubo, Yasushi Okada, Shoji Takada","doi":"10.1016/j.bpj.2024.09.010","DOIUrl":null,"url":null,"abstract":"Many bacteria enable locomotion by rotating their flagellum. It has been suggested that this rotation is realized by the rotary motion of the stator unit, MotAB, which is driven by proton transfer across the membrane. Recent cryo-electron microscopy studies have revealed a 5:2 MotAB configuration, in which a MotB dimer is encircled by a ring-shaped MotA pentamer. Although the structure implicates the rotary motion of the MotA wheel around the MotB axle, the molecular mechanisms of rotary motion and how they are coupled with proton transfer across the membrane remain elusive. In this study, we built a structure-based computational model for <ce:italic>Campylobacter jejuni</ce:italic> MotAB, conducted comprehensive protonation-state-dependent molecular dynamics simulations, and revealed a plausible proton-transfer-coupled rotation pathway. The model assumes rotation-dependent proton transfer, in which proton uptake from the periplasmic side to the conserved aspartic acid in MotB is followed by proton hopping to the MotA proton-carrying site, followed by proton export to the CP. We suggest that, by maintaining two of the proton-carrying sites of MotA in the deprotonated state, the MotA pentamer robustly rotates by ∼36° per proton transfer across the membrane. Our results provide a structure-based mechanistic model of the rotary motion of MotAB in bacterial flagellar motors and provide insights into various ion-driven rotary molecular motors.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-11","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.2024.09.010","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
Many bacteria enable locomotion by rotating their flagellum. It has been suggested that this rotation is realized by the rotary motion of the stator unit, MotAB, which is driven by proton transfer across the membrane. Recent cryo-electron microscopy studies have revealed a 5:2 MotAB configuration, in which a MotB dimer is encircled by a ring-shaped MotA pentamer. Although the structure implicates the rotary motion of the MotA wheel around the MotB axle, the molecular mechanisms of rotary motion and how they are coupled with proton transfer across the membrane remain elusive. In this study, we built a structure-based computational model for Campylobacter jejuni MotAB, conducted comprehensive protonation-state-dependent molecular dynamics simulations, and revealed a plausible proton-transfer-coupled rotation pathway. The model assumes rotation-dependent proton transfer, in which proton uptake from the periplasmic side to the conserved aspartic acid in MotB is followed by proton hopping to the MotA proton-carrying site, followed by proton export to the CP. We suggest that, by maintaining two of the proton-carrying sites of MotA in the deprotonated state, the MotA pentamer robustly rotates by ∼36° per proton transfer across the membrane. Our results provide a structure-based mechanistic model of the rotary motion of MotAB in bacterial flagellar motors and provide insights into various ion-driven rotary molecular motors.
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.