Reactome | GBP1:GTP binds LPS on the bacterial surface

GBP1:GTP binds LPS on the bacterial surface

Stable Identifier

R-HSA-9947932

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, peptidoglycan-based cell wall

ReviewStatus

5/5

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GBP1:GTP binds LPS on the bacterial surface

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Guanylate-binding protein 1 (GBP1) localizes to the lipopolysaccharide (LPS)-rich outer membranes of cytosolic Gram-negative bacteria in GTP-dependent manner (Kutsch M et al., 2020; Santos JC et al., 2020). It binds bacterial LPS with high affinity through electrostatic interactions. Membrane association of GBP1 depends largely on the accessibility of its farnesyl tail (Shydlovskyi S et al., 2017). In its inactive state without nucleotides, GBP1 is a monomer with the farnesyl group sequestered within a hydrophobic pocket, preventing membrane interaction. GTP binding to GBP1 triggers structural shifts enabling exposure of the farnesyl moiety of GBP1 for membrane interaction, GTPase activation, and oligomerization of GBP1 on bacterial membranes (Shydlovskyi S et al., 2017; Sistemich L et al., 2021; Ince S et al., 2021; Weismehl M et al., 2024; Kuhm T et al., 2025).

Literature References

PubMed ID	Title	Journal	Year
33405388	Structural requirements for membrane binding of human guanylate-binding protein 1 Sistemich, L, Dimitrov Stanchev, L, Kutsch, M, Roux, A, Günther Pomorski, T, Herrmann, C	FEBS J	2021
28645896	Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1 Shydlovskyi, S, Zienert, AY, Ince, S, Dovengerds, C, Hohendahl, A, Dargazanli, JM, Blum, A, Günther, SD, Kladt, N, Stürzl, M, Schauss, AC, Kutsch, M, Roux, A, Praefcke, GJK, Herrmann, C	Proc Natl Acad Sci U S A	2017
32581219	Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria Santos, JC, Boucher, D, Schneider, LK, Demarco, B, Dilucca, M, Shkarina, K, Heilig, R, Chen, KW, Lim, RYH, Broz, P	Nat Commun	2020
38267655	Structural insights into the activation mechanism of antimicrobial GBP1 Weismehl, M, Chu, X, Kutsch, M, Lauterjung, P, Herrmann, C, Kudryashev, M, Daumke, O	EMBO J	2024
39394410	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
32510692	Direct binding of polymeric GBP1 to LPS disrupts bacterial cell envelope functions Kutsch, M, Sistemich, L, Lesser, CF, Goldberg, MB, Herrmann, C, Coers, J	EMBO J	2020