Das synthetische Chaperon 4-PBA induziert eine Akut-Phase-Reaktion im Maus-Modell für Protein-Speicherkrankheiten

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
F Schneider ◽  
Y Churin ◽  
A Köppel ◽  
KM Baier ◽  
A Tschuschner ◽  
...  
Keyword(s):  
Fur Protein

Was unterscheidet die Subtypen der Creutzfeldt-Jakob-Krankheit von anderen Demenzen mit initialen psychiatrischen Auffälligkeiten?

2003 ◽  
Vol 01 (01) ◽  
pp. 24-29
Author(s):  
H. Wormstall ◽  
M. Bartels ◽  
G.W. Eschweiler
Keyword(s):  
Tau Protein ◽  
Fur Protein ◽  
T2 Mri ◽  
Codon 129

ZusammenfassungSeit dem Nachweis boviner spongiformer Enzephalopathie (BSE) unter Rindern in Deutschland im November 2000 ist die Gefahr, an der neuen Variante der Creutzfeld-Jakob-Krankheit (vCJD) zu erkranken, auch hierzulande größer geworden. Diese Übersicht schildert die Differenzialdiagnostik von Demenzerkrankungen mit initialen psychiatrischen Auffälligkeiten im jüngeren und höheren Alter. Besonderer Wert wird auf die Unterschiede zwischen der sporadischen Creutzfeld-Jakob-Krankheit (sCJD) und der vCJD gelegt. Neben den klinischen und initial meist psychiatrisch geprägten Verläufen werden neuere laborchemische, molekulargenetische und neuroradiologische Aspekte dieser beiden Prionkrankheiten dargestellt. Der Liquor ist in den meisten Fällen positiv für Protein 14-3-3, Tau-Protein und Neuron-spezifische Enolase (NSE). Nur bei bestimmten molekulargenetisch am Codon 129 des Prionproteins determinierten Subgruppen der sCJD-Patienten, nicht aber bei vCJD-Patienten, finden sich im EEG periodische scharfe Wellen. In der Frühdiagnostik der sCJD kann vor allem die diffusionsgewichtete MRI eingesetzt werden. Bei den jüngeren vCJD-Patienten findet man neben den psychiatrischen Symptomen Parästhesien, erst später eine Demenz und Ataxie von mehr als 6 Monaten Dauer sowie T2-MRI-Signalhyperintensitäten im Pulvinar. Als weitere Differenzialdiagnosen der verschiedenen CJD-Subtypen wird auch die wenig bekannte Hashimoto-Enzephalopathie näher beschrieben.

scholarly journals Iron-Responsive Repression of Urease Expression in Helicobacter hepaticus Is Mediated by the Transcriptional Regulator Fur

2006 ◽  
Vol 75 (2) ◽  
pp. 745-752 ◽  
Author(s):  
Clara Belzer ◽  
Bart A. M. van Schendel ◽  
Ernst J. Kuipers ◽  
Johannes G. Kusters ◽  
Arnoud H. M. van Vliet
Keyword(s):  
Urease Activity ◽  
Transcriptional Regulator ◽  
Mammalian Host ◽  
Transcriptional Level ◽  
Helicobacter Hepaticus ◽  
Mucosal Surfaces ◽  
Insertional Inactivation ◽  
Fur Protein ◽  
Colonization Factors ◽  
Gene Recombinant

ABSTRACT Persistent colonization of mucosal surfaces by bacteria in the mammalian host requires concerted expression of colonization factors, depending on the environmental conditions. Helicobacter hepaticus is a urease-positive pathogen that colonizes the intestinal and hepatobiliary tracts of rodents. Here it is reported that urease expression of H. hepaticus is iron repressed by the transcriptional regulator Fur. Iron restriction of growth medium resulted in a doubling of urease activity in wild-type H. hepaticus strain ATCC 51449 and was accompanied by increased levels of urease subunit proteins and ureA mRNA. Insertional inactivation of the fur gene abolished iron-responsive repression of urease activity, whereas inactivation of the perR gene did not affect iron-responsive regulation of urease activity. The iron-responsive promoter element was identified directly upstream of the H. hepaticus ureA gene. Recombinant H. hepaticus Fur protein bound to this ureA promoter region in a metal-dependent matter, and binding resulted in the protection of a 41-bp, Fur box-containing operator sequence located at positions −35 to −75 upstream of the transcription start site. In conclusion, H. hepaticus Fur controls urease expression at the transcriptional level in response to iron availability. This represents a novel type of urease regulation in ureolytic bacteria and extends the already diverse regulatory repertoire of the Fur protein.

scholarly journals Positive Regulation of fur Gene Expression via Direct Interaction of Fur in a Pathogenic Bacterium, Vibrio vulnificus

2007 ◽  
Vol 189 (7) ◽  
pp. 2629-2636 ◽  
Author(s):  
Hyun-Jung Lee ◽  
So Hyun Bang ◽  
Kyu-Ho Lee ◽  
Soon-Jung Park
Keyword(s):  
Gene Expression ◽  
Pathogenic Bacteria ◽  
Vibrio Vulnificus ◽  
Iron Concentration ◽  
Direct Interaction ◽  
Repeated Sequence ◽  
Upstream Region ◽  
Fur Protein

ABSTRACT In pathogenic bacteria, the ability to acquire iron, which is mainly regulated by the ferric uptake regulator (Fur), is essential to maintain growth as well as its virulence. In Vibrio vulnificus, a human pathogen causing gastroenteritis and septicemia, fur gene expression is positively regulated by Fur when the iron concentration is limited (H.-J. Lee et al., J. Bacteriol. 185:5891-5896, 2003). Footprinting analysis revealed that an upstream region of the fur gene was protected by the Fur protein from DNase I under iron-depleted conditions. The protected region, from −142 to −106 relative to the transcription start site of the fur gene, contains distinct AT-rich repeats. Mutagenesis of this repeated sequence resulted in abolishment of binding by Fur. To confirm the role of this cis-acting element in Fur-mediated control of its own gene in vivo, fur expression was monitored in V. vulnificus strains using a transcriptional fusion containing the mutagenized Fur-binding site (fur mt::luxAB). Expression of fur mt::luxAB showed that it was not regulated by Fur and was not influenced by iron concentration. Therefore, this study demonstrates that V. vulnificus Fur acts as a positive regulator under iron-limited conditions by direct interaction with the fur upstream region.

scholarly journals Ferric uptake regulator (Fur) reversibly binds a [2Fe-2S] cluster to sense intracellular iron homeostasis in Escherichia coli

2020 ◽  
Vol 295 (46) ◽  
pp. 15454-15463 ◽  
Author(s):  
Chelsey R. Fontenot ◽  
Homyra Tasnim ◽  
Kathryn A. Valdes ◽  
Codrina V. Popescu ◽  
Huangen Ding
Keyword(s):  
Escherichia Coli ◽  
Iron Content ◽  
Iron Homeostasis ◽  
Ferric Uptake Regulator ◽  
Intracellular Iron ◽  
Free Iron ◽  
E Coli ◽  
Genes Encoding ◽  
Fur Protein ◽  
Mutant Cells

The ferric uptake regulator (Fur) is a global transcription factor that regulates intracellular iron homeostasis in bacteria. The current hypothesis states that when the intracellular “free” iron concentration is elevated, Fur binds ferrous iron, and the iron-bound Fur represses the genes encoding for iron uptake systems and stimulates the genes encoding for iron storage proteins. However, the “iron-bound” Fur has never been isolated from any bacteria. Here we report that the Escherichia coli Fur has a bright red color when expressed in E. coli mutant cells containing an elevated intracellular free iron content because of deletion of the iron–sulfur cluster assembly proteins IscA and SufA. The acid-labile iron and sulfide content analyses in conjunction with the EPR and Mössbauer spectroscopy measurements and the site-directed mutagenesis studies show that the red Fur protein binds a [2Fe-2S] cluster via conserved cysteine residues. The occupancy of the [2Fe-2S] cluster in Fur protein is ∼31% in the E. coli iscA/sufA mutant cells and is decreased to ∼4% in WT E. coli cells. Depletion of the intracellular free iron content using the membrane-permeable iron chelator 2,2´-dipyridyl effectively removes the [2Fe-2S] cluster from Fur in E. coli cells, suggesting that Fur senses the intracellular free iron content via reversible binding of a [2Fe-2S] cluster. The binding of the [2Fe-2S] cluster in Fur appears to be highly conserved, because the Fur homolog from Hemophilus influenzae expressed in E. coli cells also reversibly binds a [2Fe-2S] cluster to sense intracellular iron homeostasis.

scholarly journals An ABC Transporter System of Yersinia pestis Allows Utilization of Chelated Iron by Escherichia coliSAB11

1998 ◽  
Vol 180 (5) ◽  
pp. 1135-1147 ◽  
Author(s):  
Scott W. Bearden ◽  
Teanna M. Staggs ◽  
Robert D. Perry
Keyword(s):  
Yersinia Pestis ◽  
Cell Envelope ◽  
Binding Protein ◽  
Growth Stimulation ◽  
Iron Chelator ◽  
In Vitro Transcription ◽  
Cosmid Library ◽  
Atp Binding ◽  
Fur Protein

ABSTRACT The acquisition of iron is an essential component in the pathogenesis of Yersinia pestis, the agent of bubonic and pneumonic plague. A cosmid library derived from the genomic DNA ofY. pestis KIM6+ was used for transduction of anEscherichia coli mutant (SAB11) defective in the biosynthesis of the siderophore enterobactin. Recombinant plasmids which had a common 13-kb BamHI fragment were isolated from SAB11 transductants in which growth but not enterobactin synthesis was restored on media containing the iron chelator EDDA [ethylenediamine-di(o-hydroxyphenyl acetic acid)]. Subcloning and transposon mutagenesis revealed a 5.6-kb region, designated yfe, essential for SAB11 growth stimulation. In vitro transcription-translation analysis identified polypeptides of 18, 29.5, 32, and 33 kDa encoded by the yfe locus. Sequence analysis shows this locus to be comprised of five genes in two separate operons which have potential Fur-binding sequences in both promoters. A putative polycistronic operon, yfeABCD, is Fur regulated and responds to iron and manganese. A functional Fur protein is required for the observed manganese repression of this operon. This operon encodes polypeptides which have strong similarity to the ATP-binding cassette (ABC) family of transporters and include a periplasmic binding protein (YfeA), an ATP-binding protein (YfeB), and two integral membrane proteins (YfeC and -D), which likely function in the acquisition of inorganic iron and possibly other ions. The ∼21-kDa protein encoded by the separately transcribedyfeE gene may be located in the cell envelope, since ayfeE::TnphoA fusion is PhoA+. Mutations in this gene abrogate growth of SAB11 on iron-chelated media.

scholarly journals Genetic Characterization of Wild-Type and Mutantfur Genes of Bordetella avium

1999 ◽  
Vol 67 (6) ◽  
pp. 3160-3165 ◽  
Author(s):  
Erin R. Murphy ◽  
Amy Dickenson ◽  
Kevin T. Militello ◽  
Terry D. Connell
Keyword(s):  
Copy Number ◽  
Essential Element ◽  
Mutant Gene ◽  
Respiratory Pathogen ◽  
Nutritional Requirement ◽  
Wild Type ◽  
Bordetella Avium ◽  
Fur Protein ◽  
Cloned Gene

ABSTRACT For most, if not all, organisms, iron (Fe) is an essential element. In response to the nutritional requirement for Fe, bacteria evolved complex systems to acquire the element from the environment. The genes encoding these systems are often coordinately regulated in response to the Fe concentration. Recent investigations revealed thatBordetella avium, a respiratory pathogen of birds, expressed a number of Fe-regulated genes (T. D. Connell, A. Dickenson, A. J. Martone, K. T. Militello, M. J. Filiatraut, M. L. Hayman, and J. Pitula, Infect. Immun. 66:3597–3605, 1998). By using manganese selection on an engineered strain of B. avium that carried an Fe-regulated alkaline phosphatase reporter gene, a mutant was obtained that was affected in expression of Fe-regulated genes. To determine if Fe-dependent regulation in B. avium was mediated by afur-like gene, a fragment of the B. aviumchromosome, corresponding to the fur locus of B. pertussis, was cloned by PCR. Sequencing revealed that the fragment from B. avium encoded a polypeptide with 92% identity to the Fur protein of B. pertussis. In vivo experiments showed that the cloned gene complemented H1780, afur mutant of Escherichia coli. Southern hybridizations and PCRs demonstrated that the manganese mutant had a deletion of 2 to 3 kbp of nucleotide sequence in the region located immediately 5′ of the fur open reading frame. A spontaneous PCR-derived mutant of the B. avium fur gene was isolated that encoded a Fur protein in which a histidine was substituted for an arginine at amino acid position 18 (R18H). Genetic analysis showed that the R18H mutant gene when cloned into a low-copy-number vector did not complement the fur mutation in H1780. However, the R18H mutant gene was able to complement the fur mutation when cloned into a high-copy-number vector. The cloned wild-typefur gene will be useful as a genetic tool to identify Fur-regulated genes in the B. avium chromosome.

Maßgeschneiderte Liganden für Protein-Protein-Interaktionen

BIOspektrum ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. 387-389
Author(s):  
Christian Heid ◽  
Kyra Kujawski ◽  
Thomas Schrader
Keyword(s):  
Fur Protein

scholarly journals A Dominant-Negative fur Mutation in Bradyrhizobium japonicum

2004 ◽  
Vol 186 (5) ◽  
pp. 1409-1414 ◽  
Author(s):  
Heather P. Benson ◽  
Kristin LeVier ◽  
Mary Lou Guerinot
Keyword(s):  
Bradyrhizobium Japonicum ◽  
Iron Uptake ◽  
Outer Membrane Proteins ◽  
Dominant Negative ◽  
Ferric Uptake Regulator ◽  
Null Mutant ◽  
Nitrogen Fixing ◽  
Wild Type ◽  
Fur Protein

ABSTRACT In many bacteria, the ferric uptake regulator (Fur) protein plays a central role in the regulation of iron uptake genes. Because iron figures prominently in the agriculturally important symbiosis between soybean and its nitrogen-fixing endosymbiont Bradyrhizobium japonicum, we wanted to assess the role of Fur in the interaction. We identified a fur mutant by selecting for manganese resistance. Manganese interacts with the Fur protein and represses iron uptake genes. In the presence of high levels of manganese, bacteria with a wild-type copy of the fur gene repress iron uptake systems and starve for iron, whereas fur mutants fail to repress iron uptake systems and survive. The B. japonicum fur mutant, as expected, fails to repress iron-regulated outer membrane proteins in the presence of iron. Unexpectedly, a wild-type copy of the fur gene cannot complement the fur mutant. Expression of the fur mutant allele in wild-type cells leads to a fur phenotype. Unlike a B. japonicum fur-null mutant, the strain carrying the dominant-negative fur mutation is unable to form functional, nitrogen-fixing nodules on soybean, mung bean, or cowpea, suggesting a role for a Fur-regulated protein or proteins in the symbiosis.

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