Lipopolysaccharide chain length and coat assembly keep guanylate-binding proteins upright on bacterial membranes
- 1Forschungszentrum Juelich
Abstract
Guanylate-binding proteins (GBPs) defend host cells by assembling on intracellular pathogen membranes. For human GBP1, this requires a switch from a compact, closed conformation to an extended, open one, whereas for murine orthologues the open state is not known. How the open state behaves at a membrane has remained inaccessible to experiment. Using all-atom and coarse-grained molecular dynamics simulations covering over 0.5 ms, we followed human GBP1 and murine GBP2 as monomers, dimers, and higher-order assemblies on phosphatidylcholine membranes, Shigella flexneri lipopolysaccharide (LPS), and phosphoinositide-containing bilayers. Closed GBPs dock through their prenyl anchor with minimal lipid selectivity. Open GBPs, by contrast, are intrinsically unstable: monomers fold back into membrane-bound resting states, and dimers tip over unless supported, either by long LPS O-antigen chains or by neighboring molecules within a coat. The open state thus appears to be maintained not by the nucleotide alone but by the protein's molecular environment.
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BibTeX
@misc{bundschuh2026lipopolysaccharide,
title = {{Lipopolysaccharide chain length and coat assembly keep guanylate-binding proteins upright on bacterial membranes}},
author = {B. F. Bundschuh and J. Loschwitz and B. Strodel},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762752},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762752v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Lipopolysaccharide chain length and coat assembly keep guanylate-binding proteins upright on bacterial membranes
AU - B. F. Bundschuh
AU - J. Loschwitz
AU - B. Strodel
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762752
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762752v1
AB - Guanylate-binding proteins (GBPs) defend host cells by assembling on intracellular pathogen membranes. For human GBP1, this requires a switch from a compact, closed conformation to an extended, open one, whereas for murine orthologues the open state is not known. How the open state behaves at a membrane has remained inaccessible to experiment. Using all-atom and coarse-grained molecular dynamics simulations covering over 0.5 ms, we followed human GBP1 and murine GBP2 as monomers, dimers, and higher-order assemblies on phosphatidylcholine membranes, Shigella flexneri lipopolysaccharide (LPS), and phosphoinositide-containing bilayers. Closed GBPs dock through their prenyl anchor with minimal lipid selectivity. Open GBPs, by contrast, are intrinsically unstable: monomers fold back into membrane-bound resting states, and dimers tip over unless supported, either by long LPS O-antigen chains or by neighboring molecules within a coat. The open state thus appears to be maintained not by the nucleotide alone but by the protein's molecular environment.
ER -