8CQB

Cryo-EM structure of the human GBP1 dimer bound to GDP-AlF3

Summary for 8CQB

• Entry DOI: 10.2210/pdb8cqb/pdb
• EMDB information: 16794
• Descriptor: Guanylate-binding protein 1, GUANOSINE-5'-DIPHOSPHATE, ALUMINUM FLUORIDE, ... (4 entities in total)
• Functional Keywords: cell-autonomous immunity, intracellular pathogens, gtpase, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 137146.20

Authors

Kuhm, T.I.,Jakobi, A.J. (deposition date: 2023-03-04, release date: 2024-03-13, Last modification date: 2025-01-29)

Primary citation

Kuhm, T.,Taisne, C.,de Agrela Pinto, C.,Gross, L.,Giannopoulou, E.A.,Huber, S.T.,Pardon, E.,Steyaert, J.,Tans, S.J.,Jakobi, A.J.
Structural basis of antimicrobial membrane coat assembly by human GBP1.
Nat.Struct.Mol.Biol., 32:172-184, 2025

PubMed Abstract: 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 α-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.

PubMed: 39394410
DOI: 10.1038/s41594-024-01400-9

Experimental method

ELECTRON MICROSCOPY (3.7 Å)