In situ structure of the flagellar export apparatus reveals membrane remodeling and lipid-mediated coupling between FlhA and the export gate
5 affiliations
- 1Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT USA
- 2Microbial Sciences Institute, Yale University, West Haven, CT USA
- 3Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC USA
- 4Department of Cell Biology, Yale School of Medicine, New Haven, CT USA
- 5Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT USA
Abstract
The transmembrane export apparatus is a conserved core of bacterial type III secretion systems shared by flagella and injectisomes. Powered by the proton-motive force (PMF), this machinery translocates protein substrates across the cytoplasmic membrane to support bacterial motility and virulence. However, how the export apparatus assembles and functions within native membranes remains poorly understood. Here, using in situ single-particle cryo-electron microscopy and cryo-electron tomography, we resolve high-resolution structures of the flagellar export apparatus within intact cells of the Lyme disease spirochete Borrelia burgdorferi. Structural and genetic analyses suggest that coordinated assembly of the export apparatus and MS-ring drives extensive deformation of the cytoplasmic membrane, generating a funnel-shaped conduit for substrate translocation. The FlhA nonamer and FliPQR–FlhB export gate lack direct transmembrane contacts and are separated by a thin, bilayer-like density, revealing a lipid-mediated interface. The conserved FlhB hinge helix extends into the FlhA tunnel and may couple PMF-driven energy transduction to substrate translocation. We further identify a conserved hydrophilic pathway within FlhA and show that key acidic residues lining this pathway are essential for export activity. Together, these findings establish a mechanistic framework for export apparatus assembly and energy transduction, providing broader insights into type III secretion.
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BibTeX
@article{yue2026situ,
title = {{In situ structure of the flagellar export apparatus reveals membrane remodeling and lipid-mediated coupling between FlhA and the export gate}},
author = {Jian Yue and Akarsh Manne and Wangbiao Guo and Huaxin Yu and Jiaqi Wang and Md Khalesur Rahman and Kathryn Lees and Hui Xu and Jack M. Botting and Md A. Motaleb and Jun Liu},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77713-8},
url = {https://doi.org/10.1038/s41467-026-77713-8},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - In situ structure of the flagellar export apparatus reveals membrane remodeling and lipid-mediated coupling between FlhA and the export gate
AU - Jian Yue
AU - Akarsh Manne
AU - Wangbiao Guo
AU - Huaxin Yu
AU - Jiaqi Wang
AU - Md Khalesur Rahman
AU - Kathryn Lees
AU - Hui Xu
AU - Jack M. Botting
AU - Md A. Motaleb
AU - Jun Liu
PY - 2026
DA - 2026/09/25
JO - Nature Communications
DO - 10.1038/s41467-026-77713-8
UR - https://doi.org/10.1038/s41467-026-77713-8
AB - The transmembrane export apparatus is a conserved core of bacterial type III secretion systems shared by flagella and injectisomes. Powered by the proton-motive force (PMF), this machinery translocates protein substrates across the cytoplasmic membrane to support bacterial motility and virulence. However, how the export apparatus assembles and functions within native membranes remains poorly understood. Here, using in situ single-particle cryo-electron microscopy and cryo-electron tomography, we resolve high-resolution structures of the flagellar export apparatus within intact cells of the Lyme disease spirochete Borrelia burgdorferi. Structural and genetic analyses suggest that coordinated assembly of the export apparatus and MS-ring drives extensive deformation of the cytoplasmic membrane, generating a funnel-shaped conduit for substrate translocation. The FlhA nonamer and FliPQR–FlhB export gate lack direct transmembrane contacts and are separated by a thin, bilayer-like density, revealing a lipid-mediated interface. The conserved FlhB hinge helix extends into the FlhA tunnel and may couple PMF-driven energy transduction to substrate translocation. We further identify a conserved hydrophilic pathway within FlhA and show that key acidic residues lining this pathway are essential for export activity. Together, these findings establish a mechanistic framework for export apparatus assembly and energy transduction, providing broader insights into type III secretion.
SN - 2041-1723
ER -