Structural characterization of FlgE2 protein from <i>Helicobacter pylori</i> hook

Loconte, Valentina; Kekez, Ivana; Matković‐Čalogović, Dubravka; Zanotti, Giuseppe

doi:10.1111/febs.14312

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Whether SpeE binds FliM in the motor complex or sequesters monomers to regulate assembly is not clear. FlgE2 was also investigated as a possible H. pylori ‐specific regulator of flagellar hook assembly . While FlgE2 has only 26% sequence identity with FlgE1, the structure revealed high similarity with FlgE1 proteins from a variety of organisms.…”

Section: Helicobacter Pylori Gastric Colonizationmentioning

confidence: 99%

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Pathogenesis of Helicobacter pylori infection

2018

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In this review, we highlight progress in the last year in characterizing known virulence factors like flagella and the Cag type IV secretion system with sophisticated structural and biochemical approaches to yield new insight on the assembly and functions of these critical virulence determinants. Several aspects of Helicobacter pylori physiology were newly explored this year and evaluated for their functions during stomach colonization, including a fascinating role for the essential protease HtrA in allowing access of H. pylori to the basolateral side of the gastric epithelium through cleavage of the tight junction protein E-cadherin to facilitate CagA delivery. Molecular biology tools standard in model bacteria, including regulated gene expression during animal infection and fluorescent reporter gene fusions, were newly applied to H. pylori to explore functions for urease beyond initial colonization and establish high salt consumption as a mediator of gene expression changes. New sequencing technologies enabled validation of long postulated roles for DNA methylation in regulating H. pylori gene expression. On the cell biology side, elegant work using lineage tracing in the murine model and organoid primary cell culture systems has provided new insights into how H. pylori manipulates gastric tissue functions, locally and at a distance, to promote its survival in the stomach and induce pathologic changes. Finally, new work has bolstered the case for genomic variation as an important mechanism to generate phenotypic diversity during changing environmental conditions in the context of diet manipulation in animal infection models and during human experimental infection after vaccination.

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Section: Helicobacter Pylori Gastric Colonizationmentioning

confidence: 99%

“…FlgE2 was also investigated as a possible H. pylorispecific regulator of flagellar hook assembly. 4 While FlgE2 has only 26% sequence identity with FlgE1, the structure revealed high similarity with FlgE1 proteins from a variety of organisms. Moreover, biochemical analysis showed FlgE2 can bind the flagellar hook cap protein FlgD.…”

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confidence: 94%

Pathogenesis of Helicobacter pylori infection

2018

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“…This work is part of our research on Helicobacter pylori proteins [ 20 , 21 ]. Our goal was to characterize Hp CrdA biophysically and structurally in a solution to consider its biophysical and structural properties and to define its function.…”

Section: Introductionmentioning

confidence: 99%

Copper Binding and Oligomerization Studies of the Metal Resistance Determinant CrdA from Helicobacter pylori

et al. 2022

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Within this research, the CrdA protein from Helicobacter pylori (HpCrdA), a putative copper-binding protein important for the survival of bacterium, was biophysically characterized in a solution, and its binding affinity toward copper was experimentally determined. Incubation of HpCrdA with Cu(II) ions favors the formation of the monomeric species in the solution. The modeled HpCrdA structure shows a conserved methionine-rich region, a potential binding site for Cu(I), as in the structures of similar copper-binding proteins, CopC and PcoC, from Pseudomonas syringae and from Escherichia coli, respectively. Within the conserved amino acid motif, HpCrdA contains two additional methionines and two glutamic acid residues (MMXEMPGMXXMXEM) in comparison to CopC and PcoCbut lacks the canonical Cu(II) binding site (two His) since the sequence has no His residues. The methionine-rich site is in a flexible loop and can adopt different geometries for the two copper oxidation states. It could bind copper in both oxidation states (I and II), but with different binding affinities, micromolar was found for Cu(II), and less than nanomolar is proposed for Cu(I). Considering that CrdA is a periplasmic protein involved in chaperoning copper export and delivery in the H. pylori cell and that the affinity of the interaction corresponds to a middle or strong metal–protein interaction depending on the copper oxidation state, we conclude that the interaction also occurs in vivo and is physiologically relevant for H. pylori.

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“…FlaA and FlaB are flagellin proteins that comprise the filament structure of flagella [ 12 , 13 ]. FlgE is a hook protein that connects the flagellar filament to the export domain of the basal body [ 14 ]. FlhA is involved in the expression regulation and export of flagellin proteins [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Hesperetin Inhibits Expression of Virulence Factors and Growth of Helicobacter pylori

Kim

Woo

Yang

et al. 2021

IJMS

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Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause various gastrointestinal diseases including gastritis and gastric cancer. Hesperetin is a major flavanone component contained in citrus fruits. It has been reported to possess antibacterial, antioxidant, and anticancer effects. However, the antibacterial mechanism of hesperetin against H. pylori has not been reported yet. Therefore, the objective of this study was to determine the inhibitory effects of hesperetin on H. pylori growth and its inhibitory mechanisms. The results of this study showed that hesperetin inhibits the growth of H. pylori reference strains and clinical isolates. Hesperetin inhibits the expression of genes in replication (dnaE, dnaN, dnaQ, and holB) and transcription (rpoA, rpoB, rpoD, and rpoN) machineries of H. pylori. Hesperetin also inhibits the expression of genes related to H. pylori motility (flhA, flaA, and flgE) and adhesion (sabA, alpA, alpB, hpaA, and hopZ). It also inhibits the expression of urease. Hespereti n downregulates major virulence factors such as cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) and decreases the translocation of CagA and VacA proteins into gastric adenocarcinoma (AGS) cells. These results might be due to decreased expression of the type IV secretion system (T4SS) and type V secretion system (T5SS) involved in translocation of CagA and VacA, respectively. The results of this study indicate that hesperetin has antibacterial effects against H. pylori. Thus, hesperetin might be an effective natural product for the eradication of H. pylori.

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Structural characterization of FlgE2 protein from Helicobacter pylori hook

Abstract: Atomic coordinates and structural factors have been deposited in the Protein Data Bank as 5NPY.

Cited by 7 publications

References 38 publications

Pathogenesis of Helicobacter pylori infection

Pathogenesis of Helicobacter pylori infection

Copper Binding and Oligomerization Studies of the Metal Resistance Determinant CrdA from Helicobacter pylori

Hesperetin Inhibits Expression of Virulence Factors and Growth of Helicobacter pylori

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