A new class of biological ion-driven rotary molecular motors with 5:2 symmetry

Rieu, Martin; Krutyholowa, Roscislaw; Taylor, Nicholas M. I.; Berry, Richard M.

doi:10.3389/fmicb.2022.948383

Cited by 17 publications

(17 citation statements)

References 147 publications

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“…S10), likely induced by the local structural rearrangement during the stator unit activation, is necessary to achieve flexibility in this region for ion transportation. This bulky hydrophobic residue is conserved not only in flagellar stator units, but also in other 5:2 rotary motors 52 , suggesting a similar directional rotation ‘reinforcement’ mechanism (Extended Data Fig. S11).…”

Section: Resultsmentioning

confidence: 95%

Mechanisms of ion selectivity and rotor coupling in the bacterial flagellar sodium-driven stator unit

Santiveri

Eguiara

et al. 2022

Preprint

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Bacteria swim using a flagellar motor that is powered by stator units. These stator units are energized by an ionic gradient across the membrane, typically proton or sodium. The presumed monodirectional rotation of the stator units allows the bidirectional rotation of the flagellar motor. However, how ion selectivity is attained, how ion transport triggers the directional rotation of the stator unit, and how the stator unit is incorporated into the motor remain largely unclear. Here we have determined by cryo-electron microscopy the structure of the Na+-driven type stator unit PomAB from the gram-negative bacterium Vibrio alginolyticus in both lipidic and detergent environments, at a resolution up to 2.5 Angstrom. The structure is in a plugged, auto-inhibited state consisting of five PomA subunits surrounding two PomB subunits. The electrostatic potential map uncovers sodium ion binding sites within the transmembrane domain, which together with functional experiments and explicit solvent molecular dynamics simulations, suggest a mechanism for ion translocation and selectivity. Resolved conformational isomers of bulky hydrophobic residues from PomA, in the vicinity of key determinant residues for sodium ion coupling of PomB, prime PomA for clockwise rotation. The rotation is tightly blocked by the trans-mode organization of the PomB plug motifs. The structure also reveals a conformationally dynamic helical motif at the C-terminus of PomA, which we propose regulates the distance between PomA subunit cytoplasmic domains and is involved in stator unit-rotor interaction, concomitant stator unit activation, and torque transmission. Together, our studies provide mechanistic insight for understanding flagellar stator unit ion selectivity and incorporation of the stator units into the motor.

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Section: Resultsmentioning

confidence: 95%

Mechanisms of ion selectivity and rotor coupling in the bacterial flagellar sodium-driven stator unit

Santiveri

Eguiara

et al. 2022

Preprint

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“…Further recent structural work has identified the basis for ion selectivity and many catalytic residues involved in the process 9 . The current consensus model is that a transmembrane pentameric ring of MotA subunits rotates around a central dimer stalk of MotB TM domains 9,10 . The model details the conformational waypoints through which the MotA subunit passes during the gating cycle of the stator, but our understanding of the dynamics, in general, is limited, and in particularly for the MotB subunit central stalk.…”

Section: Introductionmentioning

confidence: 99%

“…The central MotB dimer is important because it harbours the catalytic centre. It has been proposed to rotate in place between protonated and non-protonated states 10 . Previous work suggested that the MotB TM domains exchange their interface contacts during gating and may pivot along their helical axis 11 , in a similar fashion to the proposed mechanism for the homologous TolR protein 12 .…”

Section: Introductionmentioning

confidence: 99%

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Tuning the stator subunit of the flagellar motor with coiled-coil engineering

Ridone

Winter

Baker

2023

Preprint

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Many bacteria swim driven by an extracellular filament rotated by the bacterial flagellar motor. This motor is powered by the stator complex, MotA5MotB2, a heterodimeric complex which forms an ion channel which couples energy from the ion motive force to torque generation. Recent structural work revealed that stator complex consists of a ring of five MotAs which rotate around a central dimer of MotBs. Transmembrane (TM) domains TM3 and TM4 from MotA combine with the single TM domain from MotB to form two separate ion channels in this complex. Much is known about the ion binding site and specificity, however to-date no modelling has been undertaken to explore the MotB-MotB dimer stability and the role of MotB mobility during rotation. Here we modelled the central MotB dimer using coiled-coil engineering and modelling principles and calculated free energies (BUDE) to identify stable states in the operating cycle of the stator. We found 3 stable coiled-coil states with interface angles 28°, 56° and 64°. We tested the effect of strategic mutagenesis on the comparative energy of the states and correlated motility with a specific hierarchy of stability between the three states. In general, our results indicate agreement with existing models describing a 36° rotation step of the MotA pentameric ring during the power stroke and provide an energetic basis for the coordinated rotation of the central MotB dimer based on coiled-coil modelling.

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“…In the viruses, a rotary functionalism is supposedly involved in inserting DNA into the phage head (Firman & Youell, 2013). Besides these, 3 new proteins are recently attributed rotary functionality on the basis of structural/symmetry features (Rieu et al, 2022). Of these instances, claims for rotation have been supported with 'visual evidence' for only Complex V and BFS.…”

Section: Introduction To Bacterial Flagellar System (Bfs)mentioning

confidence: 99%

Questioning physiological rotary functionality in the bacterial flagellar system and proposing a murburn model for motility

Manoj¹,

Jacob²,

Kavdia³

et al. 2022

Preprint

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Bacterial flagellar system (BFS) was the first perceived example of a ‘natural rotary-motor” functionality, mandating the translation of a circular motion of components inside into a linear displacement of the cell body outside. This outcome is supposedly orchestrated with the following features of the BFS: (i) A chemical/electrical differential generates proton motive force (pmf, including a trans-membrane potential, TMP), which is electro-mechanically transduced by inward movement of protons via BFS. (ii) Membrane-bound roteins of BFS serve as stators and the slender filament acts as an external propeller, culminating into a hook-rod that pierces the membrane to connect to a ‘broader assembly of deterministically movable rotor’. We had disclaimed the purported pmf/TMP-based respiratory/photosynthetic physiology involving Complex V, which was also perceived as a “rotary machine” earlier. We pointed out that the murburn redox logic was operative therein. In the context of BFS, we pursue the following similar perspectives: (i) Low probability for the evolutionary attainment of an ordered/synchronized teaming of about two dozen types of proteins (assembled across five-seven distinct phases) towards the singular agendum of rotary motility. (ii) Vital redox activity (not the gambit of pmf/TMP!) powers the molecular and macroscopic activities of cells, including flagella. (iii) Flagellar movement is noted even in ambiances lacking/countering the directionality mandates sought by pmf/TMP. (iv) Structural features of BFS lack component(s) capable of harnessing/achieving pmf/TMP and functional rotation. Falling short of disproving rotability, a viable murburn model for conversion of molecular/biochemical activity into macroscopic/mechanical outcomes is proposed herein for understanding BFS-assisted motility.

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A new class of biological ion-driven rotary molecular motors with 5:2 symmetry

Cited by 17 publications

References 147 publications

Mechanisms of ion selectivity and rotor coupling in the bacterial flagellar sodium-driven stator unit

Mechanisms of ion selectivity and rotor coupling in the bacterial flagellar sodium-driven stator unit

Tuning the stator subunit of the flagellar motor with coiled-coil engineering

Questioning physiological rotary functionality in the bacterial flagellar system and proposing a murburn model for motility

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