An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA

Conradi J, Tegtmeyer N, Wozna M, Wißbrock M, Michalek C, Gagell C, Cover TL, Frank R, Sewald N, Backert S (2012)
Frontiers in Cellular and Infection Microbiology 2: 70.

Download
OA
Zeitschriftenaufsatz | Veröffentlicht | Englisch
Volltext vorhanden für diesen Nachweis
Autor
; ; ; ; ; ; ; ; ;
Abstract / Bemerkung
Helicobacter pylori is a specific gastric pathogen that colonizes the stomach in more than 50% of the world’s human population. Infection with this bacterium can induce several types of gastric pathology, ranging from chronic gastritis to peptic ulcers and even adenocarcinoma. Virulent H. pylori isolates encode components of a type IV secretion system (T4SS), which form a pilus for the injection of virulence proteins such as CagA into host target cells. This is accomplished by a specialized adhesin on the pilus surface, the protein CagL, a putative VirB5 ortholog, which binds to host cell β1 integrin, triggering subsequent delivery of CagA across the host cell membrane. Like the human extracellular matrix protein fibronectin, CagL contains an RGD (Arg-Gly-Asp) motif and is able to trigger intracellular signaling pathways by RGD-dependent binding to integrins. While CagL binding to host cells is mediated primarily by the RGD motif, we identified an auxiliary binding motif for CagL–integrin interaction. Here, we report on a surface exposed FEANE (Phe-Glu-Ala-Asn-Glu) interaction motif in spatial proximity to the RGD sequence, which enhances the interactions of CagL with integrins. It will be referred to as RGD helper sequence (RHS). Competitive cell adhesion assays with recombinant wild type CagL and point mutants, competition experiments with synthetic cyclic and linear peptides, and peptide array experiments revealed amino acids essential for the interaction of the RHS motif with integrins. Infection experiments indicate that the RHS motif plays a role in the early interaction of H. pylori T4SS with integrin, to trigger signaling and to inject CagA into host cells. We thus postulate that CagL is a versatile T4SS surface protein equipped with at least two motifs to promote binding to integrins, thereby causing aberrant signaling within host cells and facilitating translocation of CagA into host cells, thus contributing directly to H. pylori pathogenesis.
Erscheinungsjahr
Zeitschriftentitel
Frontiers in Cellular and Infection Microbiology
Band
2
Seite(n)
70
ISSN
eISSN
Finanzierungs-Informationen
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft and the Open Access Publication Fund of Bielefeld University.
PUB-ID

Zitieren

Conradi J, Tegtmeyer N, Wozna M, et al. An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA. Frontiers in Cellular and Infection Microbiology. 2012;2:70.
Conradi, J., Tegtmeyer, N., Wozna, M., Wißbrock, M., Michalek, C., Gagell, C., Cover, T. L., et al. (2012). An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA. Frontiers in Cellular and Infection Microbiology, 2, 70. doi:10.3389/fcimb.2012.00070
Conradi, J., Tegtmeyer, N., Wozna, M., Wißbrock, M., Michalek, C., Gagell, C., Cover, T. L., Frank, R., Sewald, N., and Backert, S. (2012). An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA. Frontiers in Cellular and Infection Microbiology 2, 70.
Conradi, J., et al., 2012. An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA. Frontiers in Cellular and Infection Microbiology, 2, p 70.
J. Conradi, et al., “An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA”, Frontiers in Cellular and Infection Microbiology, vol. 2, 2012, pp. 70.
Conradi, J., Tegtmeyer, N., Wozna, M., Wißbrock, M., Michalek, C., Gagell, C., Cover, T.L., Frank, R., Sewald, N., Backert, S.: An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA. Frontiers in Cellular and Infection Microbiology. 2, 70 (2012).
Conradi, Jens, Tegtmeyer, Nicole, Wozna, Marta, Wißbrock, Marco, Michalek, Carmela, Gagell, Corinna, Cover, Timothy L., Frank, Ronald, Sewald, Norbert, and Backert, Steffen. “An RGD helper sequence in CagL of Helicobacter pylori assists in interactions with integrins and injection of CagA”. Frontiers in Cellular and Infection Microbiology 2 (2012): 70.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Copyright Statement:
This Item is protected by copyright and/or related rights. [...]
Volltext(e)
Access Level
OA Open Access
Zuletzt Hochgeladen
2017-11-09T10:05:01Z

37 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis.
Román-Román A, Martínez-Santos VI, Castañón-Sánchez CA, Albañil-Muñoz AJ, González-Mendoza P, Soto-Flores DG, Martínez-Carrillo DN, Fernández-Tilapa G., Gut Pathog 11(), 2019
PMID: 30805032
Beyond the Matrix: The Many Non-ECM Ligands for Integrins.
LaFoya B, Munroe JA, Miyamoto A, Detweiler MA, Crow JJ, Gazdik T, Albig AR., Int J Mol Sci 19(2), 2018
PMID: 29393909
CagY-Dependent Regulation of Type IV Secretion in Helicobacter pylori Is Associated with Alterations in Integrin Binding.
Skoog EC, Morikis VA, Martin ME, Foster GA, Cai LP, Hansen LM, Li B, Gaddy JA, Simon SI, Solnick JV., MBio 9(3), 2018
PMID: 29764950
Unusual Manifestation of Live Staphylococcus saprophyticus, Corynebacterium urinapleomorphum, and Helicobacter pylori in the Gallbladder with Cholecystitis.
Backert S, Tegtmeyer N, Oyarzabal OA, Osman D, Rohde M, Grützmann R, Vieth M., Int J Mol Sci 19(7), 2018
PMID: 29933576
Integrin but not CEACAM receptors are dispensable for Helicobacter pylori CagA translocation.
Zhao Q, Busch B, Jiménez-Soto LF, Ishikawa-Ankerhold H, Massberg S, Terradot L, Fischer W, Haas R., PLoS Pathog 14(10), 2018
PMID: 30365569
DNA Transfer and Toll-like Receptor Modulation by Helicobacter pylori.
Varga MG, Peek RM., Curr Top Microbiol Immunol 400(), 2017
PMID: 28124154
Helicobacter pylori: A Paradigm Pathogen for Subverting Host Cell Signal Transmission.
Naumann M, Sokolova O, Tegtmeyer N, Backert S., Trends Microbiol 25(4), 2017
PMID: 28057411
Bacterial thiol oxidoreductases - from basic research to new antibacterial strategies.
Bocian-Ostrzycka KM, Grzeszczuk MJ, Banaś AM, Jagusztyn-Krynicka EK., Appl Microbiol Biotechnol 101(10), 2017
PMID: 28409380
Functional interaction and structural characteristics of unique components of Helicobacter pylori T4SS.
Merino E, Flores-Encarnación M, Aguilar-Gutiérrez GR., FEBS J 284(21), 2017
PMID: 28470874
Molecular dissection of protein-protein interactions between integrin α5β1 and the Helicobacter pylori Cag type IV secretion system.
Koelblen T, Bergé C, Cherrier MV, Brillet K, Jimenez-Soto L, Ballut L, Takagi J, Montserret R, Rousselle P, Fischer W, Haas R, Fronzes R, Terradot L., FEBS J 284(23), 2017
PMID: 29055076
In Silico Design of a Chimeric Protein Containing Antigenic Fragments of Helicobacter pylori; A Bioinformatic Approach.
Mohammad N, Karsabet MT, Amani J, Ardjmand A, Zadeh MR, Gholi MK, Saffari M, Ghasemi A., Open Microbiol J 10(), 2016
PMID: 27335622
A C-Terminal Coiled-Coil Region of CagL is Responsible for Helicobacter Pylori-Induced Il-8 Expression.
Wiedemann T, Hofbaur S, Loell E, Rieder G., Eur J Microbiol Immunol (Bp) 6(3), 2016
PMID: 27766167
Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of East Asian-type Helicobacter pylori strains.
Lind J, Backert S, Hoffmann R, Eichler J, Yamaoka Y, Perez-Perez GI, Torres J, Sticht H, Tegtmeyer N., BMC Microbiol 16(1), 2016
PMID: 27590005
Differences in amino acid frequency in CagA and VacA sequences of Helicobacter pylori distinguish gastric cancer from gastric MALT lymphoma.
Hashinaga M, Suzuki R, Akada J, Matsumoto T, Kido Y, Okimoto T, Kodama M, Murakami K, Yamaoka Y., Gut Pathog 8(), 2016
PMID: 27833662
Crystal structure of CagL from Helicobacter pylori K74 strain.
Choi JM, Choi YH, Sudhanva MS, Devakumar S, Lee KH, Cha JH, Lee SH., Biochem Biophys Res Commun 460(4), 2015
PMID: 25839651
Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways.
Yong X, Tang B, Li BS, Xie R, Hu CJ, Luo G, Qin Y, Dong H, Yang SM., Cell Commun Signal 13(), 2015
PMID: 26160167
Potential of known and short prokaryotic protein motifs as a basis for novel peptide-based antibacterial therapeutics: a computational survey.
Ruhanen H, Hurley D, Ghosh A, O'Brien KT, Johnston CR, Shields DC., Front Microbiol 5(), 2014
PMID: 24478765
Exploring alternative treatments for Helicobacter pylori infection.
Ayala G, Escobedo-Hinojosa WI, de la Cruz-Herrera CF, Romero I., World J Gastroenterol 20(6), 2014
PMID: 24587621
Helicobacter pylori and gastric cancer: Indian enigma.
Misra V, Pandey R, Misra SP, Dwivedi M., World J Gastroenterol 20(6), 2014
PMID: 24587625
Structure of a three-dimensional domain-swapped dimer of the Helicobacter pylori type IV secretion system pilus protein CagL.
Barden S, Schomburg B, Conradi J, Backert S, Sewald N, Niemann HH., Acta Crystallogr D Biol Crystallogr 70(pt 5), 2014
PMID: 24816107
Systematic analysis of phosphotyrosine antibodies recognizing single phosphorylated EPIYA-motifs in CagA of Western-type Helicobacter pylori strains.
Lind J, Backert S, Pfleiderer K, Berg DE, Yamaoka Y, Sticht H, Tegtmeyer N., PLoS One 9(5), 2014
PMID: 24800748
The impact of serine protease HtrA in apoptosis, intestinal immune responses and extra-intestinal histopathology during Campylobacter jejuni infection of infant mice.
Heimesaat MM, Fischer A, Alutis M, Grundmann U, Boehm M, Tegtmeyer N, Göbel UB, Kühl AA, Bereswill S, Backert S., Gut Pathog 6(), 2014
PMID: 24883112
The role of serine protease HtrA in acute ulcerative enterocolitis and extra-intestinal immune responses during Campylobacter jejuni infection of gnotobiotic IL-10 deficient mice.
Heimesaat MM, Alutis M, Grundmann U, Fischer A, Tegtmeyer N, Böhm M, Kühl AA, Göbel UB, Backert S, Bereswill S., Front Cell Infect Microbiol 4(), 2014
PMID: 24959425
Helicobacter pylori cell translocating kinase (CtkA/JHP0940) is pro-apoptotic in mouse macrophages and acts as auto-phosphorylating tyrosine kinase.
Tenguria S, Ansari SA, Khan N, Ranjan A, Devi S, Tegtmeyer N, Lind J, Backert S, Ahmed N., Int J Med Microbiol 304(8), 2014
PMID: 25172221
A novel NOD1- and CagA-independent pathway of interleukin-8 induction mediated by the Helicobacter pylori type IV secretion system.
Gorrell RJ, Guan J, Xin Y, Tafreshi MA, Hutton ML, McGuckin MA, Ferrero RL, Kwok T., Cell Microbiol 15(4), 2013
PMID: 23107019
Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori.
Salama NR, Hartung ML, Müller A., Nat Rev Microbiol 11(6), 2013
PMID: 23652324
A helical RGD motif promoting cell adhesion: crystal structures of the Helicobacter pylori type IV secretion system pilus protein CagL.
Barden S, Lange S, Tegtmeyer N, Conradi J, Sewald N, Backert S, Niemann HH., Structure 21(11), 2013
PMID: 24076404
Research advances in the study of Campylobacter, Helicobacter, and related organisms.
Merrell DS, Stintzi A., Front Cell Infect Microbiol 2(), 2012
PMID: 23267439

45 References

Daten bereitgestellt von Europe PubMed Central.

Grb2 is a key mediator of helicobacter pylori CagA protein activities.
Mimuro H, Suzuki T, Tanaka J, Asahi M, Haas R, Sasakawa C., Mol. Cell 10(4), 2002
PMID: 12419219
Structure of integrin alpha5beta1 in complex with fibronectin.
Takagi J, Strokovich K, Springer TA, Walz T., EMBO J. 22(18), 2003
PMID: 12970173
An improved method for the solution cyclization of peptides under pseudo-high dilution conditions.
Malesevic M, Strijowski U, Bachle D, Sewald N., J. Biotechnol. 112(1-2), 2004
PMID: 15288942
Helicobacter pylori CagL dependent induction of gastrin expression via a novel αvβ5-integrin-integrin linked kinase signalling complex.
Wiedemann T, Hofbaur S, Tegtmeyer N, Huber S, Sewald N, Wessler S, Backert S, Rieder G., Gut 61(7), 2012
PMID: 22287591
Helicobacter pylori induces AGS cell motility and elongation via independent signaling pathways.
Moese S, Selbach M, Kwok T, Brinkmann V, Konig W, Meyer TF, Backert S., Infect. Immun. 72(6), 2004
PMID: 15155677
Role of type IV secretion in Helicobacter pylori pathogenesis.
Backert S, Selbach M., Cell. Microbiol. 10(8), 2008
PMID: 18410539
The role of integrin binding sites in fibronectin matrix assembly in vivo.
Leiss M, Beckmann K, Giros A, Costell M, Fassler R., Curr. Opin. Cell Biol. 20(5), 2008
PMID: 18586094
Cyclic RGD peptides interfere with binding of the Helicobacter pylori protein CagL to integrins αVβ3 and α5β1.
Conradi J, Huber S, Gaus K, Mertink F, Royo Gracia S, Strijowski U, Backert S, Sewald N., Amino Acids 43(1), 2011
PMID: 21915696
A small fibronectin-mimicking protein from bacteria induces cell spreading and focal adhesion formation.
Tegtmeyer N, Hartig R, Delahay RM, Rohde M, Brandt S, Conradi J, Takahashi S, Smolka AJ, Sewald N, Backert S., J. Biol. Chem. 285(30), 2010
PMID: 20507990
VirB2 and VirB5 proteins: specialized adhesins in bacterial type-IV secretion systems?
Backert S, Fronzes R, Waksman G., Trends Microbiol. 16(9), 2008
PMID: 18706815
A novel sheathed surface organelle of the Helicobacter pylori cag type IV secretion system.
Rohde M, Puls J, Buhrdorf R, Fischer W, Haas R., Mol. Microbiol. 49(1), 2003
PMID: 12823823
Large-scale analysis of protein-protein interactions using cellulose-bound peptide arrays.
Beutling U, Stading K, Stradal T, Frank R., Adv. Biochem. Eng. Biotechnol. 110(), 2008
PMID: 18418558
Identification of a novel integrin binding site in fibronectin. Differential utilization by beta 3 integrins.
Bowditch RD, Hariharan M, Tominna EF, Smith JW, Yamada KM, Getzoff ED, Ginsberg MH., J. Biol. Chem. 269(14), 1994
PMID: 7511609
c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains.
Mueller D, Tegtmeyer N, Brandt S, Yamaoka Y, De Poire E, Sgouras D, Wessler S, Torres J, Smolka A, Backert S., J. Clin. Invest. 122(4), 2012
PMID: 22378042
Structural and functional characterization of the VirB5 protein from the type IV secretion system encoded by the conjugative plasmid pKM101.
Yeo HJ, Yuan Q, Beck MR, Baron C, Waksman G., Proc. Natl. Acad. Sci. U.S.A. 100(26), 2003
PMID: 14673074
Helicobacter exploits integrin for type IV secretion and kinase activation.
Kwok T, Zabler D, Urman S, Rohde M, Hartig R, Wessler S, Misselwitz R, Berger J, Sewald N, Konig W, Backert S., Nature 449(7164), 2007
PMID: 17943123
Helicobacter pylori CagL activates ADAM17 to induce repression of the gastric H, K-ATPase alpha subunit.
Saha A, Backert S, Hammond CE, Gooz M, Smolka AJ., Gastroenterology 139(1), 2010
PMID: 20303353
Helicobacter pylori type IV secretion apparatus exploits beta1 integrin in a novel RGD-independent manner.
Jimenez-Soto LF, Kutter S, Sewald X, Ertl C, Weiss E, Kapp U, Rohde M, Pirch T, Jung K, Retta SF, Terradot L, Fischer W, Haas R., PLoS Pathog. 5(12), 2009
PMID: 19997503
Coadaptation of Helicobacter pylori and humans: ancient history, modern implications.
Atherton JC, Blaser MJ., J. Clin. Invest. 119(9), 2009
PMID: 19729845
Computation and analysis of protein circular dichroism spectra.
Sreerama N, Woody RW., Meth. Enzymol. 383(), 2004
PMID: 15063656
Type IV secretion systems and their effectors in bacterial pathogenesis.
Backert S, Meyer TF., Curr. Opin. Microbiol. 9(2), 2006
PMID: 16529981
Conformation/activity studies of rationally designed potent anti-adhesive RGD peptides.
Gurrath M, Muller G, Kessler H, Aumailley M, Timpl R., Eur. J. Biochem. 210(3), 1992
PMID: 1483474
Molecular mechanisms of epithelial-barrier disruption by Helicobacter pylori.
Wessler S, Backert S., Trends Microbiol. 16(8), 2008
PMID: 18619844
Integrin signaling.
Giancotti FG, Ruoslahti E., Science 285(5430), 1999
PMID: 10446041
Host-bacterial interactions in Helicobacter pylori infection.
Amieva MR, El-Omar EM., Gastroenterology 134(1), 2008
PMID: 18166359
The RGD motif in fibronectin is essential for development but dispensable for fibril assembly.
Takahashi S, Leiss M, Moser M, Ohashi T, Kitao T, Heckmann D, Pfeifer A, Kessler H, Takagi J, Erickson HP, Fassler R., J. Cell Biol. 178(1), 2007
PMID: 17591922
Helicobacter pylori: gastric cancer and beyond.
Polk DB, Peek RM Jr., Nat. Rev. Cancer 10(6), 2010
PMID: 20495574
Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface.
Shaffer CL, Gaddy JA, Loh JT, Johnson EM, Hill S, Hennig EE, McClain MS, McDonald WH, Cover TL., PLoS Pathog. 7(9), 2011
PMID: 21909278
Calculation of protein conformation from circular dichroism.
Yang JT, Wu CS, Martinez HM., Meth. Enzymol. 130(), 1986
PMID: 3773734
Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse.
Ohnishi N, Yuasa H, Tanaka S, Sawa H, Miura M, Matsui A, Higashi H, Musashi M, Iwabuchi K, Suzuki M, Yamada G, Azuma T, Hatakeyama M., Proc. Natl. Acad. Sci. U.S.A. 105(3), 2008
PMID: 18192401
Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment and activation.
Higashi H, Nakaya A, Tsutsumi R, Yokoyama K, Fujii Y, Ishikawa S, Higuchi M, Takahashi A, Kurashima Y, Teishikata Y, Tanaka S, Azuma T, Hatakeyama M., J. Biol. Chem. 279(17), 2004
PMID: 14963045
Selective recognition of cyclic RGD peptides of NMR defined conformation by alpha IIb beta 3, alpha V beta 3, and alpha 5 beta 1 integrins.
Pfaff M, Tangemann K, Muller B, Gurrath M, Muller G, Kessler H, Timpl R, Engel J., J. Biol. Chem. 269(32), 1994
PMID: 8051114
Serine phosphorylation of cortactin controls focal adhesion kinase activity and cell scattering induced by Helicobacter pylori.
Tegtmeyer N, Wittelsberger R, Hartig R, Wessler S, Martinez-Quiles N, Backert S., Cell Host Microbe 9(6), 2011
PMID: 21669400
Specific entry of Helicobacter pylori into cultured gastric epithelial cells via a zipper-like mechanism.
Kwok T, Backert S, Schwarz H, Berger J, Meyer TF., Infect. Immun. 70(4), 2002
PMID: 11895977
Helicobacter pylori type IV secretion, host cell signalling and vaccine development.
Backert S, Churin Y, Meyer TF., Keio J Med 51 Suppl 2(), 2002
PMID: 12528929
1H NMR assignment and secondary structure of the cell adhesion type III module of fibronectin.
Baron M, Main AL, Driscoll PC, Mardon HJ, Boyd J, Campbell ID., Biochemistry 31(7), 1992
PMID: 1311202

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 22919661
PubMed | Europe PMC

Suchen in

Google Scholar