Structural basis of outer membrane biogenesis and cell division by Tol/Pal nanomachinery

TL;DR

This paper reveals the structure of the TolQRA complex in bacteria, showing how it transmits energy across membranes and could help in developing new antibiotics.

Contribution

The study provides high-resolution cryo-EM structures of TolQRA at different pH levels, revealing its asymmetric arrangement and energy transduction mechanism.

Findings

TolQRA has a 5:2:5 stoichiometry with key interaction residues between TolQ, TolR, and TolA.

The complex exhibits an asymmetric arrangement, suggesting a two-gate mechanism for proton translocation.

The findings offer insights into energy transfer in Gram-negative bacteria and potential therapeutic targets.

Abstract

TolQRA, a key member of the proton motive force (PMF) family including MotAB and ExbBD, transduces PMF from the inner membrane to the outer bacterial envelope. This mechanism compensates for the absence of conventional energy sources in the outer membrane compartment of Gram-negative bacteria. Here, we present cryo–electron microscopy structures of the TolQRA complex at pH 5.4 and pH 8.0, resolved at 3.18 and 3.60 angstroms, respectively. Our findings revealed that TolQRA has a stoichiometry of 5:2:5, with key residues mediating interactions between TolQ, TolR, and TolA. Notably, the nanomachine has appeared to exhibit an asymmetric arrangement, which may be consistent with a two-gate mechanism for proton translocation and energy transfer. These insights illuminate the mechanism of energy transduction in TolQRA, offering parallels with the ExbBD-TonB and MotAB systems. Furthermore, this work provides a foundation for the development of innovative therapeutics that target the critical TolQRA complex.

Cryo-EM structures of the TolQRA complex at pH 5.4 and pH 8.0 were resolved at 3.18 and 3.60 Å, with the stoichiometry of 5:2:5.

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