Identification of Residues in the Human Guanylate-binding Protein 1 Critical for Nucleotide Binding and Cooperative GTP Hydrolysis

Praefcke, Gerrit J. K.; Kloep, Stephan; Benscheid, Utz; Lilie, Hauke; Prakash, Balaji; Herrmann, Christian

doi:10.1016/j.jmb.2004.09.026

Cited by 116 publications

(200 citation statements)

References 54 publications

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“…The T75A and E99A mutants described here were recently identified independently by another group (36). Their studies showed that the T75A mutant is indeed a very poor catalyst of GTP hydrolysis, with a 1,500-fold decrease in specific activity relative to wildtype.…”

Section: Discussionmentioning

confidence: 59%

“…The R48P mutant behaves quite differently from a published mutant in which residue 48 is mutated to alanine. That mutant has a slightly higher affinity for the hydrolysisresistant GTP analog GppNHp (guanosine 5Ј-[␤,␥-imido] triphosphate) than wild-type hGBP-1 but loses its ability to hydrolyze GTP (36). We also generated two mutants, T75A and E99A, that bind but do not efficiently hydrolyze GTP (Fig.…”

Section: Golgi Localization Requires Active Farnesyl Transferase and mentioning

confidence: 99%

See 1 more Smart Citation

Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-γ-inducible cofactor

Modiano

Cresswell

2005

Proc. Natl. Acad. Sci. U.S.A.

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Human guanylate-binding protein-1 (hGBP-1) is a large GTPase, similar in structure to the dynamins. Like many smaller GTPases of the Ras͞Rab family, it is farnesylated, suggesting it may dock into membranes and perhaps play a role in intracellular trafficking. To date, however, hGBP-1 has never been associated with a specific intracellular compartment. Here we present evidence that hGBP-1 can associate with the Golgi apparatus. Redistribution from the cytosol to the Golgi was observed by immunofluorescence and subcellular fractionation after aluminum fluoride treatment, suggesting that it occurs when hGBP-1 is in its GTP-bound state. Relocalization was blocked by a farnesyl transferase inhibitor. The C589S mutant of hGBP-1, which cannot be farnesylated, and the previously uncharacterized R48P mutant, which cannot bind GTP, both failed to localize to the Golgi. These two mutants had a dominant-negative effect, preventing endogenous wild-type hGBP-1 from efficiently redistributing after aluminum fluoride treatment. Furthermore, hGBP-1 requires another IFN-␥-induced factor to be targeted to the Golgi, because constitutively expressed hGBP-1 remained cytosolic in cells treated with aluminum fluoride unless the cells were preincubated with IFN-␥. Finally, two nonhydrolyzing mutants of hGBP-1, corresponding to active mutants of Ras family proteins, failed to constitutively associate with the Golgi; we propose three possible explanations for this surprising result.antiviral proteins ͉ GTPases ͉ innate immunity

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Section: Discussionmentioning

confidence: 59%

Section: Golgi Localization Requires Active Farnesyl Transferase and mentioning

confidence: 99%

Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-γ-inducible cofactor

Modiano

Cresswell

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…Im GBP-1-K51A-Protein wurde eine Aminosäure an der Position +51 von GBP-1 mutiert (Lysin zu Alanin), was zu einer fast vollständigen Hemmung der GTP-Bindung und der GTPase-Aktivität führt (Praefcke et al, 2004). In der Mutante GBP-1-D184N wurde die Aminosäure Asparaginsäure an Position +184 zu Asparagin ausgetauscht, wodurch ein mutiertes GBP-1-Protein entsteht, welches nicht mehr in der Lage ist GTP zu binden (Guenzi et al, 2001;Praefcke et al, 1999).…”

Section: Itga4-expression Beteiligtunclassified

“…In ersten Untersuchungen mit HUVEC, welche GTPase-Mutanten von GBP-1 (GBP-1-K51A, GBP-1-D184N) exprimieren (Praefcke et al, 2004), konnte weiterhin gezeigt werden, dass die GTPase-Aktivität von GBP-1 für die Induktion von ITGA4 wichtig ist. Die Einführung der beiden GTPase-Mutationen in das GBP-1-Protein hatte zur Folge, dass die Aufregulation der ITGA4-Expression im Vergleich zum Wildtyp-Protein um mehr als die Hälfte niedriger war.…”

Section: Gbp-1 Induziert Die Expression Von Itga4 In Endothelzellenunclassified

Charakterisierung molekularer Mechanismen der anti-angiogenen Aktivität von GBP-1 in Endothelzellen

Weinländer

Naschberger

Lehmann

et al. 2008

Chirurgisches Forum 2008

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“…A unique feature of the GBPs is their ability to hydrolyze GTP to GDP and GMP (Praefcke et al, 2004), and four members of this gene family, GBP1, GBP3, GBP4 and GBP5, were found to be upregulated. GBP1 mRNA has been shown to be specifically induced during the midsecretory phase of the menstrual cycle in humans, which coincidences with the putative window of implantation.…”

Section: Fig 24: Overview Of Genes Known To Be Stimulated By Type I mentioning

confidence: 99%

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

Klein¹,

Bauersachs²,

Ulbrich³

et al. 2006

Reprod. Fertil. Dev.

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Early embryonic development, implantation, and maintenance of a pregnancy are critically dependent on an intact embryo-maternal communication. So far, only few signals involved in this dialogue have been identified. In ruminants, interferon tau (IFN�) plays a key role in the process of maternal recognition of pregnancy by exhibiting antiluteolytic activity. Even though many experimental findings indicate a pivotal role of IFN� in the context of embryo-maternal communication in ruminants, a number of other systems may be involved. To identify genes induced in the bovine endometrium by the signaling of the embryo, a combination of subtracted cDNA libraries and cDNA array hybridization was applied. Monozygotic twin pairs (n = 5) were used as the biological model. Pregnancy was created in one twin by transferring two in vitro-produced embryos on Day 7 of the estrous cycle; the other twin received a sham embryo transfer. Pregnant and nonpregnant twins were slaughtered at Day 18; endometrial tissue samples were recovered and processed for transcriptome analysis as described (Bauersachs et al. 2005 J. Mol. Endocrinol. 34, 889-908). Screening of 4608 clones of two subtracted libraries revealed 90 different up-regulated genes and mRNAs, of which almost 50% are known to be stimulated by type I interferons. Among these interferon-stimulated genes, the ISG15 system is assumed to be of particular interest, and several components were studied in more detail using in situ hybridization. The pattern of mRNA expression suggests that modification of endometrial proteins through ISG15ylation plays a fundamental role during the pre-implantation period. A classification of the identified genes based on Gene Ontologies revealed the prevalence of genes involved in regulation of gene expression, cell communication, cell growth, cell differentiation, cell proliferation, and cell adhesion, and also the prevalence of genes with immune-related functions. These results underline the intense response of the endometrium to the presence of a conceptus, culminating in the preparation of the maternal environment for embryonic implantation. Further, for eleven selected genes the expression in the endometrium was quantified by the use of real-time RT-PCR. Overall, the results of quantitative RT-PCR and array hybridization correlated very well. To our knowledge this study provides the first holistic gene expression analysis of the bovine endometrium during the pre-implantation period. The results underline the importance of IFN� as an embryo-derived pregnancy recognition signal and depict the molecular mechanisms at the mRNA level underlying the intense embryo-maternal dialog taking place at Day 18 of gestation.

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Identification of Residues in the Human Guanylate-binding Protein 1 Critical for Nucleotide Binding and Cooperative GTP Hydrolysis

Cited by 116 publications

References 54 publications

Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-γ-inducible cofactor

Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-γ-inducible cofactor

Charakterisierung molekularer Mechanismen der anti-angiogenen Aktivität von GBP-1 in Endothelzellen

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

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