8cqb

Publication Abstract from PubMed

Guanylate-binding proteins (GBPs) are interferon-inducible guanosine triphosphate hydrolases (GTPases) mediating host defense against intracellular pathogens. Their antimicrobial activity hinges on their ability to self-associate and coat pathogen-associated compartments or cytosolic bacteria. Coat formation depends on GTPase activity but how nucleotide binding and hydrolysis prime coat formation remains unclear. Here, we report the cryo-electron microscopy structure of the full-length human GBP1 dimer in its guanine nucleotide-bound state and describe the molecular ultrastructure of the GBP1 coat on liposomes and bacterial lipopolysaccharide membranes. Conformational changes of the middle and GTPase effector domains expose the isoprenylated C terminus for membrane association. The alpha-helical middle domains form a parallel, crossover arrangement essential for coat formation and position the extended effector domain for intercalation into the lipopolysaccharide layer of gram-negative membranes. Nucleotide binding and hydrolysis create oligomeric scaffolds with contractile abilities that promote membrane extrusion and fragmentation. Our data offer a structural and mechanistic framework for understanding GBP1 effector functions in intracellular immunity.

Structural basis of antimicrobial membrane coat assembly by human GBP1.,Kuhm T, Taisne C, de Agrela Pinto C, Gross L, Giannopoulou EA, Huber ST, Pardon E, Steyaert J, Tans SJ, Jakobi AJ Nat Struct Mol Biol. 2025 Jan;32(1):172-184. doi: 10.1038/s41594-024-01400-9. , Epub 2024 Oct 11. PMID:39394410^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.