The Highly Repetitive Region of the Helicobacter pylori CagY Protein Comprises Tandem Arrays of an α-Helical Repeat Module

Delahay, Robin M.; Balkwill, Graham D.; Bunting, Karen A.; Edwards, Wayne R.; Atherton, John C.; Searle, Mark S.

doi:10.1016/j.jmb.2008.01.053

Cited by 28 publications

(39 citation statements)

References 37 publications

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“…Expression of GST and GST-VirB10 C-terminal fusion proteins was induced with isopropyl ␤-D-thiogalactopyranoside, and the proteins were subsequently purified from clarified lysates in the presence of protease inhibitor mixture (Roche Applied Science) using glutathione-Sepharose 4 Fast Flow (GE Healthcare) according to the manufacturer's instructions. Furthermore, His-tagged VirB10 repeat proteins, VirB10 Rpt 2.1 and 2.2 from strains Q86A and 13a, respectively, were expressed and purified as described previously (39). The exact coordinates of all VirB10 fragments are given in Fig.…”

Section: Cagl Peptides and Purification Of Cagl And Virb10mentioning

confidence: 99%

A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation

Tegtmeyer

Hartig

Delahay

et al. 2010

Journal of Biological Chemistry

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104

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Eukaryotic cell adhesion is a fundamental process in tissue development, homeostasis, and disease and is mediated by specific interactions of cell surface receptors with extracellular matrix (ECM) 2 proteins (1-5). The ECM is a meshwork of fibrillar and nonfibrillar components assembled into complex structures such as basement membranes. The latter provide a scaffold for cell adhesion, spreading, and migration. ECM regulates numerous cell functions by activating multiple signaling pathways at the adhesion sites. ECMs, composed of collagens, laminins, and other glycoproteins such as fibronectin (FN), serve as substrates for different adhesion molecules including the integrin family of transmembrane receptors. The assembly of ECM components into functional supramolecular modules is highly regulated (3-7). FN matrix assembly alone is a dynamic cell-driven process in which the soluble FN molecules assemble into insoluble fibrillar polymeric ECM structures (8).FN and integrin receptors play crucial roles in a variety of morphogenetic processes, which are regulated by processes termed outside-in and inside-out signaling cascades (3-5). Deregulation of integrin and FN functions associates with disease development including chronic inflammation, heart failure, cancer, and metastasis (7, 9 -11). The outside-in signaling triggered by ligation of integrin receptors with FN and other ECM components results in the reorganization of cytoskeletal and signaling molecules into complexes of more than 90 proteins (9 -13). This occurs by synergistic processes dependent on integrin aggregation and occupancy, as well as tyrosine phosphorylation. Integrins also cooperate with growth factor receptors such as epidermal growth factor receptor (EGFR) to enhance signaling (14).FN consists of multiple domains (classified types I-III) that show binding specificities for specific cell membrane receptors, collagen, fibrin, and heparin. FN alone is sufficient to induce highly efficient spreading of many mammalian cell types including fibroblast and epithelial cells in vitro. An important functional unit of FN is its RGD tripeptide motif, which acts in

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Section: Cagl Peptides and Purification Of Cagl And Virb10mentioning

confidence: 99%

A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation

Tegtmeyer

Hartig

Delahay

et al. 2010

Journal of Biological Chemistry

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104

100

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“…It is most commonly present and functional (24), containing approximately 30 genes, including those that collectively encode a type IV secretion system (T4SS) - a hollow conduit that connects the cytoplasm of the bacterial and host epithelial cells (10) (S6). This is beautifully designed for the human stomach: an antigenically variable, acid-stable structural protein (CagY) coats the "syringe," conferring stability and allowing evasion from the host immune response (25,26). Subsequent contact of the tip protein (CagL) with the epithelial cell and delivery and activation of the effector protein (CagA) stimulate local signaling and effects at the site of attachment - focal adhesions between epithelial cells (11) (Figure 2).…”

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confidence: 99%

“…CagA is polymorphic (Table 1); in particular, CagA from different H. pylori strains has different numbers and types of activating tyrosine phosphorylation motifs (TPMs), leading to different effects on cellular signaling and differing risks of disease (19)(20)(21)(22)(23). The D-type TPM found in East Asian strains binds to Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) strongly and stimulates very marked cellular effects (19,22,26). This may, in part, explain the high rate of H. pylori-associated disease in Japan and parts of China.…”

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Coadaptation of Helicobacter pylori and humans: ancient history, modern implications

2009

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Humans have been colonized by Helicobacter pylori for at least 50,000 years and probably throughout their evolution. H. pylori has adapted to humans, colonizing children and persisting throughout life. Most strains possess factors that subtly modulate the host environment, increasing the risk of peptic ulceration, gastric adenocarcinoma, and possibly other diseases. H. pylori genes encoding these and other factors rapidly evolve through mutation and recombination, changing the bacteria-host interaction. Although immune and physiologic responses to H. pylori also contribute to pathogenesis, humans have evolved in concert with the bacterium, and its recent absence throughout the life of many individuals has led to new human physiological changes. These may have contributed to recent increases in esophageal adenocarcinoma and, more speculatively, other modern diseases.

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“…The TPR repeat is a motif of ϳ34 amino acid residues frequently associated with functional protein-protein interactions in eukaryotes and prokaryotes (6,16,18,24). EnhC, another L. pneumophila TPRcontaining protein, was initially identified in strain AA100, a derivative of strain 130b, in a screen for mutants with reduced uptake by nonphagocytic HEp-2 human epidermoid carcinoma cells (14).…”

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Implication of Proteins Containing Tetratricopeptide Repeats in Conditional Virulence Phenotypes of Legionella pneumophila

et al. 2012

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Legionella pneumophila, the causative agent of Legionnaires' disease, is a ubiquitous freshwater bacterium whose virulence phenotypes require a type IV secretion system (T4SS). L. pneumophila strain JR32 contains two virulence-associated T4SSs, the Dot/ Icm and Lvh T4SSs. Defective entry and phagosome acidification phenotypes of dot/icm mutants are conditional and reversed by incubating broth-grown stationary-phase cultures in water (WS treatment) prior to infection, as a mimic of the aquatic environment of Legionella. Reversal of dot/icm virulence defects requires the Lvh T4SS and is associated with a >10-fold induction of LpnE, a tetratricopeptide repeat (TPR)-containing protein. In the current study, we demonstrated that defective entry and phagosome acidification phenotypes of mutants with changes in LpnE and EnhC, another TPR-containing protein, were similarly reversed by WS treatment. In contrast to dot/icm mutants for which the Lvh T4SS was required, reversal for the ⌬lpnE or the ⌬enhC mutant required that the other TPR-containing protein be present. The single and double ⌬lpnE and ⌬enhC mutants showed a hypersensitivity to sodium ion, a phenotype associated with dysfunction of the Dot/Icm T4SS. The ⌬lpnE single and the ⌬lpnE ⌬enhC double mutant showed 3-to 9-fold increases in translocation of Dot/Icm T4SS substrates, LegS2/SplY and LepB. Taken together, these data identify TPR-containing proteins in a second mechanism by which the WS mimic of a Legionella environmental niche can reverse virulence defects of broth-grown cultures and implicate LpnE and EnhC directly or indirectly in translocation of Dot/Icm T4SS protein substrates.

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The Highly Repetitive Region of the Helicobacter pylori CagY Protein Comprises Tandem Arrays of an α-Helical Repeat Module

Cited by 28 publications

References 37 publications

A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation

A Small Fibronectin-mimicking Protein from Bacteria Induces Cell Spreading and Focal Adhesion Formation

Coadaptation of Helicobacter pylori and humans: ancient history, modern implications

Implication of Proteins Containing Tetratricopeptide Repeats in Conditional Virulence Phenotypes of Legionella pneumophila

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