YhdP forms an envelope-spanning phospholipid-binding bridge in complex with DedD
- 1University of Oxford
Abstract
The outer membrane of Gram-negative bacteria is built from phospholipids synthesised at the inner membrane, but how they cross the periplasm remains unresolved. YhdP is the leading candidate for anterograde phospholipid transfer and is predicted to form an envelope-spanning bridge. Here we purify YhdP at endogenous levels and show by cryo-electron microscopy that it contains a continuous cavity, alongside an additional density that proteomics identifies as the cell wall-binding protein DedD. Liposome co-sedimentation shows that the C-terminal helices of YhdP bind membranes directly, and single-molecule tracking reveals that endogenous YhdP is as immobile as an outer membrane protein, indicating an envelope-spanning architecture in vivo. Native mass spectrometry demonstrates that the YhdP groove accommodates all major classes of E. coli phospholipid without headgroup preference. DedD engages YhdP through its disordered region and increases lipid density at the groove entrance, suggesting a potential role in lipid loading.
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BibTeX
@misc{tian2026yhdp,
title = {{YhdP forms an envelope-spanning phospholipid-binding bridge in complex with DedD}},
author = {Q. Tian and R. Clark and I. Musto and C. Kirschbaum and J. Mitra and B. F. Cooper and J. Szczepaniak and M. Bamber and C. V. Robinson and S. Khalid and G. Isom},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.763061},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763061v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - YhdP forms an envelope-spanning phospholipid-binding bridge in complex with DedD
AU - Q. Tian
AU - R. Clark
AU - I. Musto
AU - C. Kirschbaum
AU - J. Mitra
AU - B. F. Cooper
AU - J. Szczepaniak
AU - M. Bamber
AU - C. V. Robinson
AU - S. Khalid
AU - G. Isom
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.763061
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.763061v1
AB - The outer membrane of Gram-negative bacteria is built from phospholipids synthesised at the inner membrane, but how they cross the periplasm remains unresolved. YhdP is the leading candidate for anterograde phospholipid transfer and is predicted to form an envelope-spanning bridge. Here we purify YhdP at endogenous levels and show by cryo-electron microscopy that it contains a continuous cavity, alongside an additional density that proteomics identifies as the cell wall-binding protein DedD. Liposome co-sedimentation shows that the C-terminal helices of YhdP bind membranes directly, and single-molecule tracking reveals that endogenous YhdP is as immobile as an outer membrane protein, indicating an envelope-spanning architecture in vivo. Native mass spectrometry demonstrates that the YhdP groove accommodates all major classes of E. coli phospholipid without headgroup preference. DedD engages YhdP through its disordered region and increases lipid density at the groove entrance, suggesting a potential role in lipid loading.
ER -