title: The Gearbox of the Bacterial Flagellar Motor Switch.
abstract: Switching of flagellar motor rotation sense dictates bacterial chemotaxis. Multi-subunit FliM-FliG rotor rings couple signal protein binding in FliM with reversal of a distant FliG C-terminal (FliGC) helix involved in stator contacts. Subunit dynamics were examined in conformer ensembles generated by molecular simulations from the X-ray structures. Principal component analysis extracted collective motions. Interfacial loop immobilization by complex formation coupled elastic fluctuations of the FliM middle (FliMM) and FliG middle (FliGM) domains. Coevolved mutations captured interfacial dynamics as well as contacts. FliGM rotation was amplified via two central hinges to the FliGC helix. Intrinsic flexibility, reported by the FliGMC ensembles, reconciled conformers with opposite FliGC helix orientations. FliG domain stacking deformed the inter-domain linker and reduced flexibility; but conformational changes were not triggered by engineered linker deletions that cause a rotation-locked phenotype. These facts suggest that binary rotation states arise from conformational selection by stacking interactions.
authors.affiliation: Department of Computer Science and Synthetic Biology Theme, Brunel University London, Uxbridge UB8 3PH, UK; Computational Cell and Molecular Biology, The Francis Crick Institute, London NW1 1AT, UK.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pandini
authors.affiliation: Department of Biological Sciences, University of Texas at Dallas, Richardson, TX 75080, USA.
authors.forename: Faruck
authors.initials: F
authors.lastname: Morcos
authors.affiliation: Molecular Biology Consortium, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: khan@mbc-als.org.
authors.forename: Shahid
authors.initials: S
authors.lastname: Khan
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004548:Elasticity; D019143:Evolution, Molecular; D056004:Molecular Dynamics Simulation; D009154:Mutation
chemical_list: D001426:Bacterial Proteins; C075660:Flig protein, Bacteria; C066821:FliM protein, Bacteria