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Force-Generation by the Trans-Envelope Tol-Pal System.

Melissa N Webby1, Daniel P Williams-Jones1, Cara Press1

  • 1Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

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Summary
This summary is machine-generated.

The Tol-Pal system uses proton motive force to maintain outer membrane integrity in bacteria. This study proposes a mechanism where stator rotation drives conformational changes to power outer membrane events.

Keywords:
Gram-negative bacteriaTol-Palcell envelopeforce transductionouter membraneproton motive force

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Area of Science:

  • Bacterial cell envelope biogenesis
  • Protein-protein interactions
  • Energy transduction mechanisms

Background:

  • The Tol-Pal system is crucial for Gram-negative bacterial outer membrane (OM) integrity, utilizing proton motive force (PMF).
  • Its role in OM maintenance during cell division and as an import pathway for bacteriocins and phages is established.
  • The precise mechanism of energy transduction from the inner membrane (IM) to the OM remains elusive due to limited structural data.

Purpose of the Study:

  • To elucidate the mechanism of energy transduction by the Tol-Pal system.
  • To understand how PMF at the IM is coupled to mechanical work at the OM.
  • To provide a structural and mechanistic model for Tol-Pal function.

Main Methods:

  • Integrated in silico protein modeling with existing structural data of Tol-Pal sub-complexes.
  • Utilized mutagenesis, crosslinking, and co-conservation analysis.
  • Combined computational, in vitro, and in vivo experimental data.

Main Results:

  • Proposed a force generation mechanism involving PMF-driven rotary motion within the TolQ-TolR stator.
  • Demonstrated that stator motion induces conformational changes in the TolA helical hairpin domain.
  • This mechanism enables TolA to interact with and actuate the TolB-Pal complex at the OM.

Conclusions:

  • The study presents a novel mechanistic model for Tol-Pal-mediated energy transduction.
  • This model explains how PMF drives OM-related processes, including Pal release for cell wall binding.
  • The findings offer insights into bacterial envelope biogenesis and potential antimicrobial targets.