The Gearbox of the Bacterial Flagellar Motor Switch

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 (FliG(C)) 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 (FliM(M)) and FliG middle (FliG(M)) domains. Coevolved mutations captured interfacial dynamics as well as contacts. FliG(M) rotation was amplified via two central hinges to the FliG(C) helix. Intrinsic flexibility, reported by the FliG(MC) ensembles, reconciled conformers with opposite FliG(C) 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.