7e58

Structural highlights

Function

GBP2_HUMAN Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:31091448). Hydrolyzes GTP to GMP in 2 consecutive cleavage reactions, but the major reaction product is GDP (PubMed:8706832). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (By similarity). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (By similarity). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (By similarity). Confers protection to the protozoan pathogen Toxoplasma gondii (By similarity). Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity, such as HIV-1, Zika and influenza A viruses, by inhibiting FURIN-mediated maturation of viral envelope proteins (PubMed:31091448).[UniProtKB:Q9Z0E6]^{[1] [2]}

See Also

• GTP-binding protein 3D structures

References

1. ↑ Braun E, Hotter D, Koepke L, Zech F, Groß R, Sparrer KMJ, Müller JA, Pfaller CK, Heusinger E, Wombacher R, Sutter K, Dittmer U, Winkler M, Simmons G, Jakobsen MR, Conzelmann KK, Pöhlmann S, Münch J, Fackler OT, Kirchhoff F, Sauter D. Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins. Cell Rep. 2019 May 14;27(7):2092-2104.e10. PMID:31091448 doi:10.1016/j.celrep.2019.04.063
2. ↑ Neun R, Richter MF, Staeheli P, Schwemmle M. GTPase properties of the interferon-induced human guanylate-binding protein 2. FEBS Lett. 1996 Jul 15;390(1):69-72. PMID:8706832 doi:10.1016/0014-5793(96)00628-x
3. ↑ Cui W, Braun E, Wang W, Tang J, Zheng Y, Slater B, Li N, Chen C, Liu Q, Wang B, Li X, Duan Y, Xiao Y, Ti R, Hotter D, Ji X, Zhang L, Cui J, Xiong Y, Sauter D, Wang Z, Kirchhoff F, Yang H. Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins. Proc Natl Acad Sci U S A. 2021 Apr 13;118(15):e2022269118. PMID:33876762 doi:10.1073/pnas.2022269118