Catalytic activity of human guanylate-binding protein 1 coupled to the release of structural restraints imposed by the C-terminal domain.
Binding Sites
Biocatalysis
Cloning, Molecular
Crystallography, X-Ray
Escherichia coli
/ genetics
GTP-Binding Proteins
/ chemistry
Gene Expression
Genetic Vectors
/ chemistry
Guanosine 5'-O-(3-Thiotriphosphate)
/ chemistry
Guanosine Diphosphate
/ chemistry
Guanosine Triphosphate
/ chemistry
Humans
Kinetics
Models, Molecular
Mutation
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Multimerization
Recombinant Proteins
/ chemistry
Substrate Specificity
aluminum fluoride
guanylate-binding protein
intramolecular interactions
large GTPase
protein-protein interaction
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
05
02
2020
revised:
10
04
2020
accepted:
27
04
2020
pubmed:
1
5
2020
medline:
22
6
2021
entrez:
1
5
2020
Statut:
ppublish
Résumé
Human guanylate-binding protein 1 (hGBP-1) shows a dimer-induced acceleration of the GTPase activity yielding GDP as well as GMP. While the head-to-head dimerization of the large GTPase (LG) domain is well understood, the role of the rest of the protein, particularly of the GTPase effector domain (GED), in dimerization and GTP hydrolysis is still obscure. In this study, with truncations and point mutations on hGBP-1 and by means of biochemical and biophysical methods, we demonstrate that the intramolecular communication between the LG domain and the GED (LG:GED) is crucial for protein dimerization and dimer-stimulated GTP hydrolysis. In the course of GTP binding and γ-phosphate cleavage, conformational changes within hGBP-1 are controlled by a chain of amino acids ranging from the region near the nucleotide-binding pocket to the distant LG:GED interface and lead to the release of the GED from the LG domain. This opening of the structure allows the protein to form GED:GED contacts within the dimer, in addition to the established LG:LG interface. After releasing the cleaved γ-phosphate, the dimer either dissociates yielding GDP as the final product or it stays dimeric to further cleave the β-phosphate yielding GMP. The second phosphate cleavage step, that is, the formation of GMP, is even more strongly coupled to structural changes and thus more sensitive to structural restraints imposed by the GED. Altogether, we depict a comprehensive mechanism of GTP hydrolysis catalyzed by hGBP-1, which provides a detailed molecular understanding of the enzymatic activity connected to large structural rearrangements of the protein. DATABASE: Structural data are available in RCSB Protein Data Bank under the accession numbers: 1F5N, 1DG3, 2B92.
Substances chimiques
GBP1 protein, human
0
Recombinant Proteins
0
Guanosine Diphosphate
146-91-8
Guanosine 5'-O-(3-Thiotriphosphate)
37589-80-3
Guanosine Triphosphate
86-01-1
GTP-Binding Proteins
EC 3.6.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
582-599Informations de copyright
© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Olszewski MA, Gray J & Vestal DJ (2006) In silico genomic analysis of the human and murine guanylate-binding protein (GBP) gene clusters. J Interferon Cytokine Res 26, 328-352.
Praefcke GJK & McMahon HT (2004) The dynamin superfamily: universal membrane tubulation and fission molecules? Nat Rev 5, 133-147.
Cheng YS, Colonno RJ & Yin FH (1983) Interferon induction of fibroblast proteins with guanylate binding activity. J Biol Chem 258, 7746-7750.
Tripal P, Bauer M, Naschberger E, Mörtinger T, Hohenadl C, Cornali E, Thurau M & Stürzl M (2007) Unique features of different members of the human guanylate-binding protein family. J Interferon Cytokine Res 27, 44-52.
Lubeseder-Martellato C, Guenzi E, Jörg A, Töpolt K, Naschberger E, Kremmer E, Zietz C, Tschachler E, Hutzler P, Schwemmle M et al. (2002) Guanylate-binding protein-1 expression is selectively induced by inflammatory cytokines and is an activation marker of endothelial cells during inflammatory diseases. Am J Pathol 161, 1749-1759.
Krapp C, Hotter D, Gawanbacht A, McLaren PJ, Kluge SF, Stürzel CM, Mack K, Reith E, Engelhart S, Ciuffi A et al. (2016) Guanylate Binding Protein (GBP) 5 is an interferon-inducible inhibitor of HIV-1 infectivity. Cell Host Microbe 19, 504-514.
Itsui Y, Sakamoto N, Kakinuma S, Nakagawa M, Sekine-Osajima Y, Tasaka-Fujita M, Nishimura-Sakurai Y, Suda G, Karakama Y, Mishima K et al. (2009) Antiviral effects of the interferon-induced protein guanylate binding protein 1 and its interaction with the hepatitis C virus NS5B protein. Hepatology 50, 1727-1737.
Nordmann A, Wixler L, Boergeling Y, Wixler V & Ludwig S (2012) A new splice variant of the human guanylate-binding protein 3 mediates anti-influenza activity through inhibition of viral transcription and replication. FASEB J 26, 1290-1300.
Zhu Z, Shi Z, Yan W, Wei J, Shao D, Deng X, Wang S, Li B, Tong G & Ma Z (2013) Nonstructural protein 1 of influenza A virus interacts with human guanylate-binding protein 1 to antagonize antiviral activity. PLoS ONE 8, e55920.
Pan W, Zuo X, Feng T, Shi X & Dai J (2012) Guanylate-binding protein 1 participates in cellular antiviral response to dengue virus. Virol J 9, 292.
Al-Zeer MA, Al-Younes HM, Lauster D, Abu Lubad M & Meyer TF (2013) Autophagy restricts Chlamydia trachomatis growth in human macrophages via IFNG-inducible guanylate binding proteins. Autophagy 9, 50-62.
Tietzel I, El-Haibi C & Carabeo RA (2009) Human guanylate binding proteins potentiate the anti-chlamydia effects of interferon-gamma. PLoS ONE 4, e6499.
Wandel MP, Pathe C, Werner EI, Ellison CJ, Boyle KB, von der Malsburg A, Rohde J & Randow F (2017) GBPs inhibit motility of Shigella flexneri but are targeted for degradation by the bacterial ubiquitin ligase IpaH9.8. Cell Host Microbe 22, 507-518.e5.
Piro AS, Hernandez D, Luoma S, Feeley EM, Finethy R, Yirga A, Frickel EM, Lesser CF & Coers J (2017) Detection of cytosolic Shigella flexneri via a C-terminal triple-arginine motif of GBP1 inhibits actin-based motility. MBio 8, e01979-e01917.
Shenoy AR, Wellington DA, Kumar P, Kassa H, Booth CJ, Cresswell P & MacMicking JD (2012) GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals. Science 336, 481-485.
Guenzi E, Töpolt K, Cornali E, Lubeseder-Martellato C, Jörg A, Matzen K, Zietz C, Kremmer E, Nappi F, Schwemmle M et al. (2001) The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokines. EMBO J 20, 5568-5577.
Guenzi E, Töpolt K, Lubeseder-Martellato C, Jörg A, Naschberger E, Benelli R, Albini A & Stürzl M (2003) The guanylate binding protein-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expression. EMBO J 22, 3772-3782.
Britzen-Laurent N, Herrmann C, Naschberger E, Croner RS & Stürzl M (2016) Pathophysiological role of guanylate-binding proteins in gastrointestinal diseases. World J Gastroenterol 22, 6434-6443.
Britzen-Laurent N, Lipnik K, Ocker M, Naschberger E, Schellerer VS, Croner RS, Vieth M, Waldner M, Steinberg P, Hohenadl C & et al. (2013) GBP-1 acts as a tumor suppressor in colorectal cancer cells. Carcinogenesis 34, 153-162.
Tipton AR, Nyabuto GO, Trendel JA, Mazur TM, Wilson JP, Wadi S, Justinger JS, Moore GL, Nguyen PT & Vestal DJ (2016) Guanylate-Binding Protein-1 protects ovarian cancer cell lines but not breast cancer cell lines from killing by paclitaxel. Biochem Biophys Res Commun 478, 1617-1623.
Fukumoto M, Amanuma T, Kuwahara Y, Shimura T, Suzuki M, Mori S, Kumamoto H, Saito Y, Ohkubo Y, Duan Z et al. (2014) Guanine nucleotide-binding protein 1 is one of the key molecules contributing to cancer cell radioresistance. Cancer Sci 105, 1351-1359.
Praefcke GJK (2018) Regulation of innate immune functions by guanylate-binding proteins. Int J Med Microbiol 308, 237-245.
Daumke O & Praefcke GJK (2016) Invited review: mechanisms of GTP hydrolysis and conformational transitions in the dynamin superfamily. Biopolymers 105, 580-593.
Prakash B, Praefcke GJ, Renault L, Wittinghofer A & Herrmann C (2000) Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature 403, 567-571.
Prakash B, Renault L, Praefcke GJK, Herrmann C & Wittinghofer A (2000) Triphosphate structure of guanylate-binding protein 1 and implications for nucleotide binding and GTPase mechanism. EMBO J 19, 4555-4564.
Ghosh A, Praefcke GJK, Renault L, Wittinghofer A & Herrmann C (2006) How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP. Nature 440, 101-104.
Schwemmle M & Staeheli P (1994) The interferon-induced 67-kDa guanylate-binding protein (hGBP1) is a GTPase that converts GTP to GMP. J Biol Chem 269, 11299-11305.
Kunzelmann S, Praefcke GJK & Herrmann C (2005) Nucleotide binding and self-stimulated GTPase activity of human guanylate-binding protein 1 (hGBP1). Methods Enzymol 404, 512-527.
Kunzelmann S, Praefcke GJK & Herrmann C (2006) Transient kinetic investigation of GTP hydrolysis catalyzed by interferon-gamma-induced hGBP1 (human guanylate binding protein 1). J Biol Chem 281, 28627-28635.
Abdullah N, Balakumari M & Sau AK (2010) Dimerization and its role in GMP formation by human guanylate binding proteins. Biophys J 99, 2235-2244.
Praefcke GJK, Kloep S, Benscheid U, Lilie H, Prakash B & Herrmann C (2004) Identification of residues in the human guanylate-binding protein 1 critical for nucleotide binding and cooperative GTP hydrolysis. J Mol Biol 344, 257-269.
Vöpel T, Syguda A, Britzen-Laurent N, Kunzelmann S, Lüdemann M-B, Dovengerds C, Stürzl M & Herrmann C (2010) Mechanism of GTPase-activity-induced self-assembly of human guanylate binding protein 1. J Mol Biol 400, 63-70.
Syguda A, Bauer M, Benscheid U, Ostler N, Naschberger E, Ince S, Stürzl M & Herrmann C (2012) Tetramerization of human guanylate-binding protein 1 is mediated by coiled-coil formation of the C-terminal α-helices. FEBS J 279, 2544-2554.
Ince S, Kutsch M, Shydlovskyi S & Herrmann C (2017) The human guanylate-binding proteins hGBP-1 and hGBP-5 cycle between monomers and dimers only. FEBS J 284, 2284-2301.
Wehner M, Kunzelmann S & Herrmann C (2012) The guanine cap of human guanylate-binding protein 1 is responsible for dimerization and self-activation of GTP hydrolysis. FEBS J 279, 203-210.
Shydlovskyi S, Zienert AY, Ince S, Dovengerds C, Hohendahl A, Dargazanli JM, Blum A, Günther SD, Kladt N, Stürzl M et al. (2017) Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1. Proc Natl Acad Sci USA 114, E5559-E5568.
Modiano N, Lu YE & Cresswell P (2005) Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor. Proc Natl Acad Sci USA 102, 8680-8685.
Ji C, Du S, Li P, Zhu Q, Yang X, Long C & Yu J (2019) Structural mechanism for guanylate-binding proteins (GBPs) targeting by the Shigella E3 ligase IpaH9.8. PLoS Pathog 15, e1007876.
Rani A, Pandita E, Rahman S, Deep S & Sau AK (2012) Insight into temperature dependence of GTPase activity in human guanylate binding protein-1. PLoS ONE 7, e40487.
Kutsch M, Ince S & Herrmann C (2018) Homo and hetero dimerisation of the human guanylate-binding proteins hGBP-1 and hGBP-5 characterised by affinities and kinetics. FEBS J 285, 2019-2036.
Wittinghofer A & Vetter IR (2011) Structure-function relationships of the G domain, a canonical switch motif. Annu Rev Biochem 80, 943-971.
Britzen-Laurent N, Bauer M, Berton V, Fischer N, Syguda A, Reipschläger S, Naschberger E, Herrmann C & Stürzl M (2010) Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner. PLoS ONE 5, e14246.
Naschberger E, Bauer M & Stürzl M (2005) Human guanylate binding protein-1 (hGBP-1) characterizes and establishes a non-angiogenic endothelial cell activation phenotype in inflammatory diseases. Adv Enzyme Regul 45, 215-227.
Sistemich L, Kutsch M, Hämisch B, Zhang P, Shydlovskyi S, Britzen-Laurent N, Stürzl M, Huber K & Herrmann C (2020) The molecular mechanism of polymer formation of farnesylated human guanylate-binding protein 1. J Mol Biol. 432 :2164-2185.
Grek S, Davis J & Blaber M (2001) An efficient, flexible-model program for the analysis of differential scanning calorimetry protein denaturation data. Protein Pept Lett 8, 429-436.