GBP-mediated host defense

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PMID: 38422126; PMCID: PMC12091997.; Weismehl M, Chu X, Kutsch M, Lauterjung P, Herrmann C, Kudryashev M, Daumke O. Structural insights into the activation mechanism of antimicrobial GBP1. EMBO J. 2024 Jan 24;43(4):615–36. doi: 10.1038/s44318-023-00023-y.; Fisch D, Pfleiderer MM, Anastasakou E, Mackie GM, Wendt F, Liu X, Clough B, Lara-Reyna S, Encheva V, Snijders AP, Bando H, Yamamoto M, Beggs AD, Mercer J, Shenoy AR, Wollscheid B, Maslowski KM, Galej WP, Frickel EM. PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection. Science. 2023 Oct 06;382(6666):eadg2253. PMID: 37797010; PMCID: PMC7615196.; Dickinson MS, Kutsch M, Sistemich L, Hernandez D, Piro AS, Needham D, Lesser CF, Herrmann C, Coers J. LPS-aggregating proteins GBP1 and GBP2 are each sufficient to enhance caspase-4 activation both in cellulo and in vitro. Proc Natl Acad Sci U S A. 2023 Apr 11;120(15):e2216028120. PMID: 37023136; PMCID: PMC10104521.; Mesner D, Reuschl AK, Whelan MVX, Bronzovich T, Haider T, Thorne LG, Ragazzini R, Bonfanti P, Towers GJ, Jolly C. SARS-CoV-2 evolution influences GBP and IFITM sensitivity. Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2212577120. PMID: 36693093; PMCID: PMC9945951.; Valeva SV, Degabriel M, Michal F, Gay G, Rohde JR, Randow F, Lagrange B, Henry T. Comparative study of GBP recruitment on two cytosol-dwelling pathogens, Francisella novicida and Shigella flexneri highlights differences in GBP repertoire and in GBP1 motif requirements. Pathog Dis. 2023 Jan 17;81(). doi: 10.1093/femspd/ftad005. PMID: 37012222.; Kutsch M, González-Prieto C, Lesser CF, Coers J. The GBP1 microcapsule interferes with IcsA-dependent septin cage assembly around Shigella flexneri. Pathog Dis. 2021 Apr 24;79(5). PMID: 33885766; PMCID: PMC8068759.; 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). PMID: 33876762; PMCID: PMC8054025.; Sistemich L, Dimitrov Stanchev L, Kutsch M, Roux A, Günther Pomorski T, Herrmann C. Structural requirements for membrane binding of human guanylate-binding protein 1. FEBS J. 2021 Jul;288(13):4098–114. doi: 10.1111/febs.15703. PMID: 33405388.; Kutsch M, Coers J. Human guanylate binding proteins: nanomachines orchestrating host defense. The FEBS Journal. 2021 Jan 12;288(20):5826–49. doi: 10.1111/febs.15662.; Santos JC, Boucher D, Schneider LK, Demarco B, Dilucca M, Shkarina K, Heilig R, Chen KW, Lim RYH, Broz P. Human GBP1 binds LPS to initiate assembly of a caspase-4 activating platform on cytosolic bacteria. Nature Communications. 2020 Jun 24;11(1):3276. doi: 10.1038/s41467-020-16889-z.; Wandel MP, Kim B, Park E, Boyle KB, Nayak K, Lagrange B, Herod A, Henry T, Zilbauer M, Rohde J, MacMicking JD, Randow F. Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms. Nature Immunology. 2020 Jun 15;21(8):880–91. doi: 10.1038/s41590-020-0697-2.; Kutsch M, Sistemich L, Lesser CF, Goldberg MB, Herrmann C, Coers J. Direct binding of polymeric GBP1 to LPS disrupts bacterial cell envelope functions. EMBO J. 2020 Jul 01;39(13):e104926. PMID: 32510692; PMCID: PMC7327485.; Xavier A, Al-Zeer MA, Meyer TF, Daumke O. hGBP1 Coordinates Chlamydia Restriction and Inflammasome Activation through Sequential GTP Hydrolysis. Cell Rep. 2020 May 19;31(7):107667. doi: 10.1016/j.celrep.2020.107667. PMID: 32433976.; Ince S, Zhang P, Kutsch M, Krenczyk O, Shydlovskyi S, Herrmann C. Catalytic activity of human guanylate-binding protein 1 coupled to the release of structural restraints imposed by the C-terminal domain. FEBS J. 2021 Jan;288(2):582–99. doi: 10.1111/febs.15348. PMID: 32352209.; Sistemich L, Kutsch M, Hämisch B, Zhang P, Shydlovskyi S, Britzen-Laurent N, Stürzl M, Huber K, Herrmann C. The Molecular Mechanism of Polymer Formation of Farnesylated Human Guanylate-binding Protein 1. J Mol Biol. 2020 Mar 27;432(7):2164–85. doi: 10.1016/j.jmb.2020.02.009. PMID: 32087202.; Lorenz C, Ince S, Zhang T, Cousin A, Batra-Safferling R, Nagel-Steger L, Herrmann C, Stadler AM. Farnesylation of human guanylate-binding protein 1 as safety mechanism preventing structural rearrangements and uninduced dimerization. FEBS J. 2020 Feb;287(3):496–514. doi: 10.1111/febs.15015. PMID: 31330084.; Fisch D, Bando H, Clough B, Hornung V, Yamamoto M, Shenoy AR, Frickel E. Human GBP 1 is a microbe-specific gatekeeper of macrophage apoptosis and pyroptosis. The EMBO Journal. 2019 Jun 03;38(13). doi: 10.15252/embj.2018100926.; 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. doi: 10.1016/j.celrep.2019.04.063. PMID: 31091448.; Piro AS, Hernandez D, Luoma S, Feeley EM, Finethy R, Yirga A, Frickel EM, Lesser CF, Coers J. Detection of Cytosolic Shigella flexneri via a C-Terminal Triple-Arginine Motif of GBP1 Inhibits Actin-Based Motility. mBio. 2017 Dec 29;8(6). doi: 10.1128/mbio.01979-17.; Lin X, Sun R, Zhang F, Gao Y, Bin L, Lan K. The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Inhibits Expression of SUMO/Sentrin-Specific Peptidase 6 To Facilitate Establishment of Latency. J Virol. 2017 Sep 01;91(17). PMID: 28615201; PMCID: PMC5553180.; 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. Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):E5559–68. PMID: 28645896; PMCID: PMC5514708.; Pandita E, Rajan S, Rahman S, Mullick R, Das S, Sau AK. Tetrameric assembly of hGBP1 is crucial for both stimulated GMP formation and antiviral activity. Biochem J. 2016 Jun 15;473(12):1745–57. doi: 10.1042/bcj20160220. PMID: 27071416.; 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. doi: 10.1016/j.chom.2016.02.019. PMID: 26996307.; Persico M, Petrella L, Orteca N, Di Dato A, Mariani M, Andreoli M, De Donato M, Scambia G, Novellino E, Ferlini C, Fattorusso C. GTP is an allosteric modulator of the interaction between the guanylate-binding protein 1 and the prosurvival kinase PIM1. European Journal of Medicinal Chemistry. 2015 Feb;91():132–44. doi: 10.1016/j.ejmech.2014.07.093.; Ostler N, Britzen-Laurent N, Liebl A, Naschberger E, Lochnit G, Ostler M, Forster F, Kunzelmann P, Ince S, Supper V, Praefcke GJK, Schubert DW, Stockinger H, Herrmann C, Stürzl M. Gamma Interferon-Induced Guanylate Binding Protein 1 Is a Novel Actin Cytoskeleton Remodeling Factor. Molecular and Cellular Biology. 2014 Jan 01;34(2):196–209. doi: 10.1128/mcb.00664-13.; Britzen-Laurent N, Bauer M, Berton V, Fischer N, Syguda A, Reipschläger S, Naschberger E, Herrmann C, Stürzl M. Intracellular Trafficking of Guanylate-Binding Proteins Is Regulated by Heterodimerization in a Hierarchical Manner. PLoS ONE. 2010 Dec 07;5(12):e14246. doi: 10.1371/journal.pone.0014246.; Ghosh A, Praefcke GJ, Renault L, Wittinghofer A, Herrmann C. How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP. Nature. 2006 Mar 02;440(7080):101–4. doi: 10.1038/nature04510. PMID: 16511497.; Prakash B, Praefcke GJ, Renault L, Wittinghofer A, Herrmann C. Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature. 2000 Feb 03;403(6769):567–71. doi: 10.1038/35000617. PMID: 10676968.; Nantais DE, Schwemmle M, Stickney JT, Vestal DJ, Buss JE. Prenylation of an interferon-gamma-induced GTP-binding protein: the human guanylate binding protein, huGBP1. J Leukoc Biol. 1996 Sep;60(3):423–31. doi: 10.1002/jlb.60.3.423. PMID: 8830800.; Schwemmle M, Staeheli P. The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a GTPase that converts GTP to GMP. Journal of Biological Chemistry. 1994 Apr;269(15):11299–305. doi: 10.1016/s0021-9258(19)78125-3.

Metabolites



Enzyme

EC Number name full name note
3.6.5.-
2.5.1.58 protein farnesyltransferase farnesyl-diphosphate:protein-cysteine farnesyltransferase
2.5.1.59 protein geranylgeranyltransferase type I geranylgeranyl-diphosphate:protein-cysteine geranyltransferase
3.4.21.75 Furin


Proteins

Protein ID name full name