Lipopolysaccharide chain length and coat assembly keep guanylate-binding proteins upright on bacterial membranes

Open human GBP1 and murine GBP2 assemblies on bacterial membranes are intrinsically unstable, with monomers folding back and dimers tipping unless supported by long LPS O-antigen or neighboring coat proteins.

• Why it matters: The open conformation needed for GBP coat assembly is hard to test experimentally on membranes, leaving uncertainty about how murine orthologues behave in realistic lipid and LPS contexts.
• What they did: Using all-atom and coarse-grained molecular dynamics simulations totaling over 0.5 ms, the study tracked human GBP1 and murine GBP2 monomers, dimers, and higher-order assemblies on phosphatidylcholine membranes, Shigella flexneri LPS, and phosphoinositide-containing bilayers.
• The result: Closed GBPs dock via their prenyl anchor with minimal lipid selectivity, while open states persist only when the molecular environment—long LPS O-antigen chains or adjacent coat members—stabilizes them.

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