7e5a

Structural highlights

Function

GBP5_HUMAN Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (By similarity). Hydrolyzes GTP, but in contrast to other family members, does not produce GMP (PubMed:20180847). 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). As an activator of NLRP3 inflammasome assembly: promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). 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:26996307, PubMed:31091448).[UniProtKB:Q8CFB4]^{[1] [2] [3] [4]} Antigenic tumor-specific truncated splice form.^[5]

See Also

• GTP-binding protein 3D structures

References

1. ↑ Wehner M, Herrmann C. Biochemical properties of the human guanylate binding protein 5 and a tumor-specific truncated splice variant. FEBS J. 2010 Apr;277(7):1597-605. PMID:20180847 doi:10.1111/j.1742-4658.2010.07586.x
2. ↑ Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P, MacMicking JD. GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science. 2012 Apr 27;336(6080):481-5. PMID:22461501 doi:10.1126/science.1217141
3. ↑ Krapp C, Hotter D, Gawanbacht A, McLaren PJ, Kluge SF, Stürzel CM, Mack K, Reith E, Engelhart S, Ciuffi A, Hornung V, Sauter D, Telenti A, Kirchhoff F. Guanylate Binding Protein (GBP) 5 Is an Interferon-Inducible Inhibitor of HIV-1 Infectivity. Cell Host Microbe. 2016 Apr 13;19(4):504-14. PMID:26996307 doi:10.1016/j.chom.2016.02.019
4. ↑ 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
5. ↑ Fellenberg F, Hartmann TB, Dummer R, Usener D, Schadendorf D, Eichmüller S. GBP-5 splicing variants: New guanylate-binding proteins with tumor-associated expression and antigenicity. J Invest Dermatol. 2004 Jun;122(6):1510-7. PMID:15175044 doi:10.1111/j.0022-202X.2004.22613.x
6. ↑ 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