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Yersinia virulence depends on mimicry of host Rho-family nucleotide dissociation inhibitors.

Prehna G, Ivanov MI, Bliska JB, Stebbins CE
Cell 126 869-80 (2006)
Cited: 81 times
EuropePMC logo PMID: 16959567

Abstract

Yersinia spp. cause gastroenteritis and the plague, representing historically devastating pathogens that are currently an important biodefense and antibiotic resistance concern. A critical virulence determinant is the Yersinia protein kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA possesses a Rac1 binding domain that mimics host guanidine nucleotide dissociation inhibitors (GDIs) of the Rho GTPases. YpkA inhibits nucleotide exchange in Rac1 and RhoA, and mutations that disrupt the YpkA-GTPase interface abolish this activity in vitro and impair in vivo YpkA-induced cytoskeletal disruption. In cell culture experiments, the kinase and the GDI domains of YpkA act synergistically to promote cytoskeletal disruption, and a Y. pseudotuberculosis mutant lacking YpkA GDI activity shows attenuated virulence in a mouse infection assay. We conclude that virulence in Yersinia depends strongly upon mimicry of host GDI proteins by YpkA.

Articles - 2h7o mentioned but not cited (5)

  1. Protein-protein docking benchmark version 3.0. Hwang H, Pierce B, Mintseris J, Janin J, Weng Z. Proteins 73 705-709 (2008)
  2. Yersinia effector YopO uses actin as bait to phosphorylate proteins that regulate actin polymerization. Lee WL, Grimes JM, Robinson RC. Nat Struct Mol Biol 22 248-255 (2015)
  3. SLIM: A Short-Linked, Highly Redox-Stable Trityl Label for High-Sensitivity In-Cell EPR Distance Measurements. Fleck N, Heubach CA, Hett T, Haege FR, Bawol PP, Baltruschat H, Schiemann O. Angew Chem Int Ed Engl 59 9767-9772 (2020)
  4. Binding interface prediction by combining protein-protein docking results. Hwang H, Vreven T, Weng Z. Proteins 82 57-66 (2014)
  5. Site Selective and Efficient Spin Labeling of Proteins with a Maleimide-Functionalized Trityl Radical for Pulsed Dipolar EPR Spectroscopy. Jassoy JJ, Heubach CA, Hett T, Bernhard F, Haege FR, Hagelueken G, Schiemann O. Molecules 24 E2735 (2019)


Reviews citing this publication (34)

  1. Regulation of small GTPases by GEFs, GAPs, and GDIs. Cherfils J, Zeghouf M. Physiol Rev 93 269-309 (2013)
  2. Manipulation of host-cell pathways by bacterial pathogens. Bhavsar AP, Guttman JA, Finlay BB. Nature 449 827-834 (2007)
  3. Functional domains and motifs of bacterial type III effector proteins and their roles in infection. Dean P. FEMS Microbiol Rev 35 1100-1125 (2011)
  4. Debugging how bacteria manipulate the immune response. Sansonetti PJ, Di Santo JP. Immunity 26 149-161 (2007)
  5. Post-translational modifications in host cells during bacterial infection. Ribet D, Cossart P. FEBS Lett 584 2748-2758 (2010)
  6. Yersinia outer proteins: Yops. Trosky JE, Liverman AD, Orth K. Cell Microbiol 10 557-565 (2008)
  7. Subversion of trafficking, apoptosis, and innate immunity by type III secretion system effectors. Raymond B, Young JC, Pallett M, Endres RG, Clements A, Frankel G. Trends Microbiol 21 430-441 (2013)
  8. Subversion of cell signaling by pathogens. Alto NM, Orth K. Cold Spring Harb Perspect Biol 4 a006114 (2012)
  9. Yersinia pestis and plague: an updated view on evolution, virulence determinants, immune subversion, vaccination, and diagnostics. Demeure CE, Dussurget O, Mas Fiol G, Le Guern AS, Savin C, Pizarro-Cerdá J. Genes Immun 20 357-370 (2019)
  10. Hijacking of Rho GTPases during bacterial infection. Lemichez E, Aktories K. Exp Cell Res 319 2329-2336 (2013)
  11. Translocated effectors of Yersinia. Matsumoto H, Young GM. Curr Opin Microbiol 12 94-100 (2009)
  12. Interactions of bacterial effector proteins with host proteins. Mattoo S, Lee YM, Dixon JE. Curr Opin Immunol 19 392-401 (2007)
  13. Bacterial serine/threonine protein kinases in host-pathogen interactions. Canova MJ, Molle V. J Biol Chem 289 9473-9479 (2014)
  14. What pathogens have taught us about posttranslational modifications. Salomon D, Orth K. Cell Host Microbe 14 269-279 (2013)
  15. Biochemical functions of Yersinia type III effectors. Shao F. Curr Opin Microbiol 11 21-29 (2008)
  16. Inhibition and termination of physiological responses by GTPase activating proteins. Ligeti E, Welti S, Scheffzek K. Physiol Rev 92 237-272 (2012)
  17. Bacterial factors exploit eukaryotic Rho GTPase signaling cascades to promote invasion and proliferation within their host. Popoff MR. Small GTPases 5 e28209 (2014)
  18. Actin dynamics in host-pathogen interaction. Stradal TEB, Schelhaas M. FEBS Lett 592 3658-3669 (2018)
  19. Coiled-coils in type III secretion systems: structural flexibility, disorder and biological implications. Gazi AD, Charova SN, Panopoulos NJ, Kokkinidis M. Cell Microbiol 11 719-729 (2009)
  20. Yersinia type III effectors perturb host innate immune responses. Pha K, Navarro L. World J Biol Chem 7 1-13 (2016)
  21. Yersinia pestis: mechanisms of entry into and resistance to the host cell. Ke Y, Chen Z, Yang R. Front Cell Infect Microbiol 3 106 (2013)
  22. Recent insights into Pasteurella multocida toxin and other G-protein-modulating bacterial toxins. Wilson BA, Ho M. Future Microbiol 5 1185-1201 (2010)
  23. Tipping the balance by manipulating post-translational modifications. Broberg CA, Orth K. Curr Opin Microbiol 13 34-40 (2010)
  24. The secreted kinase ROP18 defends Toxoplasma's border. Fentress SJ, Sibley LD. Bioessays 33 693-700 (2011)
  25. How Bacteria Subvert Animal Cell Structure and Function. Jimenez A, Chen D, Alto NM. Annu Rev Cell Dev Biol 32 373-397 (2016)
  26. Immunomodulatory Yersinia outer proteins (Yops)-useful tools for bacteria and humans alike. Grabowski B, Schmidt MA, Rüter C. Virulence 8 1124-1147 (2017)
  27. Mimicking small G-proteins: an emerging theme from the bacterial virulence arsenal. Alto NM. Cell Microbiol 10 566-575 (2008)
  28. Structural basis of eukaryotic cell targeting by type III secretion system (T3SS) effectors. Tosi T, Pflug A, Discola KF, Neves D, Dessen A. Res Microbiol 164 605-619 (2013)
  29. The pyrin inflammasome and the Yersinia effector interaction. Malik HS, Bliska JB. Immunol Rev 297 96-107 (2020)
  30. Review of computational methods for virus-host protein interaction prediction: a case study on novel Ebola-human interactions. Halder AK, Dutta P, Kundu M, Basu S, Nasipuri M. Brief Funct Genomics 17 381-391 (2018)
  31. Lost after translation: post-translational modifications by bacterial type III effectors. Salomon D, Orth K. Curr Opin Microbiol 16 213-220 (2013)
  32. α-Helices in the Type III Secretion Effectors: A Prevalent Feature with Versatile Roles. Gazi AD, Kokkinidis M, Fadouloglou VE. Int J Mol Sci 22 5412 (2021)
  33. Role of the Yersinia pseudotuberculosis Virulence Plasmid in Pathogen-Phagocyte Interactions in Mesenteric Lymph Nodes. Bliska JB, Brodsky IE, Mecsas J. EcoSal Plus 9 eESP00142021 (2021)
  34. Role of Host Small GTPases in Apicomplexan Parasite Infection. Paone S, Olivieri A. Microorganisms 10 1370 (2022)

Articles citing this publication (42)

  1. The S. Typhimurium effector SopE induces caspase-1 activation in stromal cells to initiate gut inflammation. Müller AJ, Hoffmann C, Galle M, Van Den Broeke A, Heikenwalder M, Falter L, Misselwitz B, Kremer M, Beyaert R, Hardt WD. Cell Host Microbe 6 125-136 (2009)
  2. Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Ohlson MB, Huang Z, Alto NM, Blanc MP, Dixon JE, Chai J, Miller SI. Cell Host Microbe 4 434-446 (2008)
  3. Identification of a molecular target for the Yersinia protein kinase A. Navarro L, Koller A, Nordfelth R, Wolf-Watz H, Taylor S, Dixon JE. Mol Cell 26 465-477 (2007)
  4. Structural basis of Fic-mediated adenylylation. Xiao J, Worby CA, Mattoo S, Sankaran B, Dixon JE. Nat Struct Mol Biol 17 1004-1010 (2010)
  5. Delineation of regions of the Yersinia YopM protein required for interaction with the RSK1 and PRK2 host kinases and their requirement for interleukin-10 production and virulence. McPhee JB, Mena P, Bliska JB. Infect Immun 78 3529-3539 (2010)
  6. Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation. Shang W, Jiang Y, Boettcher M, Ding K, Mollenauer M, Liu Z, Wen X, Liu C, Hao P, Zhao S, McManus MT, Wei L, Weiss A, Wang H. Proc Natl Acad Sci U S A 115 E4051-E4060 (2018)
  7. The Irish potato famine pathogen Phytophthora infestans translocates the CRN8 kinase into host plant cells. van Damme M, Bozkurt TO, Cakir C, Schornack S, Sklenar J, Jones AM, Kamoun S. PLoS Pathog 8 e1002875 (2012)
  8. Post-translational modification of the deubiquitinating enzyme otubain 1 modulates active RhoA levels and susceptibility to Yersinia invasion. Edelmann MJ, Kramer HB, Altun M, Kessler BM. FEBS J 277 2515-2530 (2010)
  9. Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network. Yang H, Ke Y, Wang J, Tan Y, Myeni SK, Li D, Shi Q, Yan Y, Chen H, Guo Z, Yuan Y, Yang X, Yang R, Du Z. Infect Immun 79 4413-4424 (2011)
  10. Enteropathogenic Escherichia coli, Samonella, Shigella and Yersinia: cellular aspects of host-bacteria interactions in enteric diseases. Reis RS, Horn F. Gut Pathog 2 8 (2010)
  11. Sequestering of Rac by the Yersinia effector YopO blocks Fcgamma receptor-mediated phagocytosis. Groves E, Rittinger K, Amstutz M, Berry S, Holden DW, Cornelis GR, Caron E. J Biol Chem 285 4087-4098 (2010)
  12. Type III secretion decreases bacterial and host survival following phagocytosis of Yersinia pseudotuberculosis by macrophages. Zhang Y, Murtha J, Roberts MA, Siegel RM, Bliska JB. Infect Immun 76 4299-4310 (2008)
  13. Characterization of a TIR-like protein from Paracoccus denitrificans. Low LY, Mukasa T, Reed JC, Pascual J. Biochem Biophys Res Commun 356 481-486 (2007)
  14. Activity-Based Proteomic Profiling of Deubiquitinating Enzymes in Salmonella-Infected Macrophages Leads to Identification of Putative Function of UCH-L5 in Inflammasome Regulation. Kummari E, Alugubelly N, Hsu CY, Dong B, Nanduri B, Edelmann MJ. PLoS One 10 e0135531 (2015)
  15. The interplay between the Escherichia coli Rho guanine nucleotide exchange factor effectors and the mammalian RhoGEF inhibitor EspH. Wong AR, Clements A, Raymond B, Crepin VF, Frankel G. mBio 3 e00250-11 (2012)
  16. Characterization of Pyrin Dephosphorylation and Inflammasome Activation in Macrophages as Triggered by the Yersinia Effectors YopE and YopT. Medici NP, Rashid M, Bliska JB. Infect Immun 87 e00822-18 (2019)
  17. Cytotoxic necrotizing factor-Y boosts Yersinia effector translocation by activating Rac protein. Wolters M, Boyle EC, Lardong K, Trülzsch K, Steffen A, Rottner K, Ruckdeschel K, Aepfelbacher M. J Biol Chem 288 23543-23553 (2013)
  18. Manipulation of host Kruppel-like factor (KLF) function by exotoxins from diverse bacterial pathogens. O'Grady E, Mulcahy H, Adams C, Morrissey JP, O'Gara F. Nat Rev Microbiol 5 337-341 (2007)
  19. Uncovering an Important Role for YopJ in the Inhibition of Caspase-1 in Activated Macrophages and Promoting Yersinia pseudotuberculosis Virulence. Schoberle TJ, Chung LK, McPhee JB, Bogin B, Bliska JB. Infect Immun 84 1062-1072 (2016)
  20. Yersinia pestis can bypass protective antibodies to LcrV and activation with gamma interferon to survive and induce apoptosis in murine macrophages. Noel BL, Lilo S, Capurso D, Hill J, Bliska JB. Clin Vaccine Immunol 16 1457-1466 (2009)
  21. Yersinia protein kinase A phosphorylates vasodilator-stimulated phosphoprotein to modify the host cytoskeleton. Ke Y, Tan Y, Wei N, Yang F, Yang H, Cao S, Wang X, Wang J, Han Y, Bi Y, Cui Y, Yan Y, Song Y, Yang X, Du Z, Yang R. Cell Microbiol 17 473-485 (2015)
  22. Regulation of local GTP availability controls RAC1 activity and cell invasion. Bianchi-Smiraglia A, Wolff DW, Marston DJ, Deng Z, Han Z, Moparthy S, Wombacher RM, Mussell AL, Shen S, Chen J, Yun DH, O'Brien Cox A, Furdui CM, Hurley E, Feltri ML, Qu J, Hollis T, Kengne JBN, Fongang B, Sousa RJ, Kandel ME, Kandel ES, Hahn KM, Nikiforov MA. Nat Commun 12 6091 (2021)
  23. Serogroup-related escape of Yersinia enterocolitica YopE from degradation by the ubiquitin-proteasome pathway. Hentschke M, Trülzsch K, Heesemann J, Aepfelbacher M, Ruckdeschel K. Infect Immun 75 4423-4431 (2007)
  24. Structure of Salmonella effector protein SopB N-terminal domain in complex with host Rho GTPase Cdc42. Burkinshaw BJ, Prehna G, Worrall LJ, Strynadka NC. J Biol Chem 287 13348-13355 (2012)
  25. Parasites lead to evolution of robustness against gene loss in host signaling networks. Salathé M, Soyer OS. Mol Syst Biol 4 202 (2008)
  26. Comment Threonine phosphorylation times bacterial secretion. Kulasekara HD, Miller SI. Nat Cell Biol 9 734-736 (2007)
  27. Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET. Peter MF, Gebhardt C, Mächtel R, Muñoz GGM, Glaenzer J, Narducci A, Thomas GH, Cordes T, Hagelueken G. Nat Commun 13 4396 (2022)
  28. Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation. Lapaquette P, Fritah S, Lhocine N, Andrieux A, Nigro G, Mounier J, Sansonetti P, Dejean A. Elife 6 e27444 (2017)
  29. The polybasic region of Rho GTPases defines the cleavage by Yersinia enterocolitica outer protein T (YopT). Fueller F, Schmidt G. Protein Sci 17 1456-1462 (2008)
  30. Enteropathogenic Escherichia coli EspH-Mediated Rho GTPase Inhibition Results in Desmosomal Perturbations. Roxas JL, Monasky RC, Roxas BAP, Agellon AB, Mansoor A, Kaper JB, Vedantam G, Viswanathan VK. Cell Mol Gastroenterol Hepatol 6 163-180 (2018)
  31. Regulation of Yersinia protein kinase A (YpkA) kinase activity by multisite autophosphorylation and identification of an N-terminal substrate-binding domain in YpkA. Pha K, Wright ME, Barr TM, Eigenheer RA, Navarro L. J Biol Chem 289 26167-26177 (2014)
  32. Targeting plague virulence factors: a combined machine learning method and multiple conformational virtual screening for the discovery of Yersinia protein kinase A inhibitors. Hu X, Prehna G, Stebbins CE. J Med Chem 50 3980-3983 (2007)
  33. Yersinia effector protein (YopO)-mediated phosphorylation of host gelsolin causes calcium-independent activation leading to disruption of actin dynamics. Singaravelu P, Lee WL, Wee S, Ghoshdastider U, Ding K, Gunaratne J, Grimes JM, Swaminathan K, Robinson RC. J Biol Chem 292 8092-8100 (2017)
  34. Structural similarity and classification of protein interaction interfaces. Zhao N, Pang B, Shyu CR, Korkin D. PLoS One 6 e19554 (2011)
  35. Mechanisms of Yersinia YopO kinase substrate specificity. Lee WL, Singaravelu P, Wee S, Xue B, Ang KC, Gunaratne J, Grimes JM, Swaminathan K, Robinson RC. Sci Rep 7 39998 (2017)
  36. Analysis of differentially expressed proteins in Yersinia enterocolitica-infected HeLa cells. Alugubelly N, Hercik K, Kibler P, Nanduri B, Edelmann MJ. Biochim Biophys Acta 1864 562-569 (2016)
  37. Congress Structures and diseases. Wendt KU, Weiss MS, Cramer P, Heinz DW. Nat Struct Mol Biol 15 117-120 (2008)
  38. Subversive bacteria reveal new tricks in their cytoskeleton-hijacking arsenal. Dominguez R. Nat Struct Mol Biol 22 178-179 (2015)
  39. The elusive activity of the Yersinia protein kinase A kinase domain is revealed. Laskowski-Arce MA, Orth K. Trends Microbiol 15 437-440 (2007)
  40. Heightened Virulence of Yersinia Is Associated with Decreased Function of the YopJ Protein. Mares CA, Lugo FP, Albataineh M, Goins BA, Newton IG, Isberg RR, Bergman MA. Infect Immun 89 e0043021 (2021)
  41. Role of Yersinia pseudotuberculosis outer proteins (Yops) in murine humoral immune response. Maia JM, Monnazzi LG, Medeiros BM. Folia Microbiol (Praha) 54 239-245 (2009)
  42. Quantitative proteomics revealed modulation of macrophages by MetQ gene of Streptococcus suis serotype 2. Pei X, Liu J, Liu M, Zhou H, Wang X, Fan H. AMB Express 10 195 (2020)


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