YspD: A Potential Therapeutic Target for Drug Design to Combat Yersinia enterocolitica Infection

  • Debjani Mandal
  • Debabrata Mandal
  • Abhishek BasuEmail author


YspD is an annotated hydrophilic translocator of Ysa–Ysp type III secretion system of Yersinia enterocolitica. YspD has sequence, secondary structure and three-dimensional structure similar to other hydrophilic translocators. All hydrophilic translocators lack transmembrane region and possess intramolecular coiled-coil region. Disordered regions are mostly clustered at the N-terminal. Large loops provide flexibility, allowing conformational changes during oligomerization and protein–protein interaction. LcrV and PcrV have globular N-terminal and C-terminal domains, connected by intramolecular coiled-coil region. YspD, IpaD, SipD and BipD lack globular N-terminal and C-terminal domains. Their N-terminal and C-terminal domain have a bundle like structure connected by the intramolecular coiled-coil. The intramolecular coiled-coil regions (helix-5&9) of YspD showed maximum conservation, followed by helices at N-terminal. Polar interactions are mainly involved during dimerization of YspD, involving polar residues from helix-9 of both the YspD molecules. A methionine forms the boundary of interaction between the two YspD molecules. The two YspD molecules are arranged in antiparallel fashion to form the dimer. N-terminal of YspB interacted with C-terminal of YspD molecule to form a pentameric complex, consisting four YspD molecules and one YspB molecule. Sequence, structural similarity and presence of specific motifs in YspD (like chaperone protein) indicate the ability of N-terminal domain to show self-chaperoning activity and regulate folding and conformational state of YspD during its journey from the bacterial cytoplasm to the needle tip. Structural analysis of YspD and its mechanism of interaction with other proteins would enable us to design drugs against this hydrophilic protein to combat Yersinia infection.


Type III secretion system Hydrophilic translocator Intramolecular coiled-coil Homology model Molecular docking Protein–protein interaction Self-chaperoning activity 



The Authors Acknowledge Dr. Saumen Datta, Principal Scientist CSIR-IICB Kolkata, for his guidance during the course of the research. Department of Biotechnology, Government of West Bengal, India provided the funding to the Department of Molecular Biology and Biotechnology, Sripat Singh College.

Compliance with Ethical Standards

Conflict of interest

All the Authors declare that they have no conflict of interest.

Research Involving Human Participants or Animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

10989_2019_9968_MOESM1_ESM.tif (32.6 mb)
Electronic supplementary material 1 Ramachandran Plot for YspD Homology Model TIFF (33,420 kb)
10989_2019_9968_MOESM2_ESM.tif (32.6 mb)
Electronic supplementary material 2 Ramachandran Plot for N-terminal deleted-YspD Homology Model (TIFF (33,420 kb)
10989_2019_9968_MOESM3_ESM.tif (32.6 mb)
Electronic supplementary material 3 Ramachandran Plot for YspB Homology Model (TIFF 33,420 kb)


  1. Ashkenazy H, Erez E, Martz E, Pupko T, Ben-Tal N (2010) ConSurf: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucl Acids Res 38(Web Server issue):W529–W533PubMedCrossRefPubMedCentralGoogle Scholar
  2. Basu A, Chatterjee R, Datta S (2012a) Expression, purification, structural and functional analysis of SycB: a type three secretion chaperone from Yersinia enterocolitica. Protein J 31:93–107PubMedCrossRefPubMedCentralGoogle Scholar
  3. Basu A, Chatterjee R, Datta S (2012b) YspC: a unique translocator exhibits structural alteration in the complex form with chaperone SycB. Protein J 31:487–498PubMedCrossRefPubMedCentralGoogle Scholar
  4. Basu A, Mandal D, Biswas M, Dhar G, Ahmed S (2017) Structural analysis of major translocator-chaperone interaction from Ysa-Ysp Type III secretion system of Yersinia enterocolitica. Int J Proteomics Bioinform 1(1):005–013Google Scholar
  5. Bottone E (1997) Yersinia enterocolitica: the charisma continues. Clin Microbiol Rev 10:257–276PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bottone E (1999) Yersinia enterocolitica: overview and epidemiologic correlates. Microbes Infect 1(4):323–333PubMedCrossRefPubMedCentralGoogle Scholar
  7. Broz P, Mueller CA, Müller SA, Philippsen A, Sorg I, Engel A, Cornelis GR (2007) Function and molecular architecture of the Yersinia injectisome tip complex. Mol Microbiol 65:1311–1320PubMedCrossRefGoogle Scholar
  8. Carter PB (1975) Pathogenecity of Yersinia enterocolitica for mice. InfectImmun 11:164–170Google Scholar
  9. Chatterjee S, Zhong D, Nordhues BA, Battaile KP, Lovell SW, De Guzman RN (2011) The crystal structure of the Salmonella type III secretion system tip protein SipD in complex with deoxycholate and chenodeoxycholate. Protein Sci 20:75–86PubMedCrossRefGoogle Scholar
  10. Chatterjee S, Chaudhury S, McShan AC, Kaur K, De Guzman RN (2013) Structure and biophysics of type III secretion in bacteria. Biochemistry 52:2508–2517PubMedPubMedCentralCrossRefGoogle Scholar
  11. Cornelis GR, Wolf-Watz H (1997) The Yersinia Yop virulon: a bacterial system for subverting eukaryotic cells. Mol Microbiol 23:861–867PubMedCrossRefGoogle Scholar
  12. Cornelis GR, Laroche Y, Balligand G, Sory MP, Wauters G (1987) Yersinia enterocolitica, a primary model for bacterial invasiveness. Rev Infect Dis 9:64–87PubMedCrossRefGoogle Scholar
  13. Cornelis GR, Boland A, Boyd AP, Geuijen C, Iriarte M, Neyt C, Sory MP, Stainier I (1998) The virulence plasmid of Yersinia, an antihost genome. Microbiol Mol Biol Rev 62:1315–1352PubMedPubMedCentralGoogle Scholar
  14. Corpet F (1988) Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res 16:10881–10890PubMedPubMedCentralCrossRefGoogle Scholar
  15. Cover TL, Aber RC (1989) Yersinia enterocolitica. N Engl J Med 321:16–24CrossRefGoogle Scholar
  16. Dey S, Anbanandam A, Mumford BE, De Guzman RN (2017) Characterization of small molecule scaffolds that bind to the Shigella type III secretion system protein IpaD. ChemMedChem 12(18):1534–1541PubMedPubMedCentralCrossRefGoogle Scholar
  17. Diepold A, Amstutz M, Abel S, Sorg I, Jenal U, Cornelis GR (2010) Deciphering the assembly of the Yersinia type III secretion injectisome. EMBO J 29:1928–1940PubMedPubMedCentralCrossRefGoogle Scholar
  18. Diepold A, Wiesand U, Cornelis GR (2011) The assembly of the export apparatus (YscR, S, T, U, V) of the Yersinia type III secretion apparatus occurs independently of other structural components and involves the formation of an YscV oligomer. Mol Microbiol 82:502–514PubMedCrossRefGoogle Scholar
  19. Drozdetskiy A, Cole C, Procter J & Barton GJ (2015) JPred4: a protein secondary structure prediction server. Nucleic Acids Res Web Server issueGoogle Scholar
  20. Foultier B, Troisfontaines P, Muller S, Opperdoes FR, Cornelis GR (2002) Characterization of the ysa pathogenicity locus in the chromosome of Yersinia enterocolitica and phylogeny analysis of type III secretion systems. J Mol Evol 55:37–51PubMedCrossRefGoogle Scholar
  21. Grutzkau A, Hanski C, Hahn H, Riecken E (1990) Involvement of M cells in the bacterial invasion of Peyer’s patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria. Gut 31:1011–1015PubMedPubMedCentralCrossRefGoogle Scholar
  22. Haller JC, Carlson S, Pederson KJ, Pierson DE (2000) A chromosomally encoded type III secretion pathway in Yersinia enterocolitica is important in virulence. Mol Microbiol 36:1436–1446PubMedCrossRefGoogle Scholar
  23. Hanski C, Kutschka U, Schmoranzer HP, Naumann M, Stallmach A, Hahn H, Menge H, Riecken EO (1989) Immunohistochemical and electron microscopic study of interaction of Yersinia enterocolitica serotype O:8 with intestinal mucosa during experimental enteritis. Infect Immun 57:673–678PubMedPubMedCentralGoogle Scholar
  24. Hauser AR (2009) The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat Reviews 7:654–665Google Scholar
  25. Hayes CS, Aoki SK, Low DA (2010) Bacterial contact-dependent delivery systems. Annu Rev Genet 44:71–90PubMedCrossRefGoogle Scholar
  26. Hueck CJ (1998) Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol Mol Biol Rev 62(2):379–433PubMedPubMedCentralGoogle Scholar
  27. Ishida T and Kinoshita K (2007) PrDOS. prediction of disordered protein regions from amino acid sequence. Nucleic Acids Res 35:Web Server issueGoogle Scholar
  28. Izore T, Job V, Dessen A (2011) Biogenesis, regulation, and targeting of the type III secretion system. Structure 19:603–612PubMedCrossRefGoogle Scholar
  29. Johnson S, Roversi P, Espina M, Olive A, Deane JE, Birket S, Field T, Picking WD, Blocker AJ, Galyov EE, Picking WL, Lea SM (2007) Self-chaperoning of the type III secretion system needle tip proteins IpaD and BipD. J Biol Chem 282:4035–4044PubMedCrossRefGoogle Scholar
  30. Jones DT (1999) Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol 292:195–202PubMedPubMedCentralCrossRefGoogle Scholar
  31. Kaur K, Chatterjee S, De Guzman RN (2016) Characterization of the Shigella and Salmonella Type III secretion system tip-translocon protein-protein interaction by paramagnetic relaxation enhancement. ChemBioChem 17(8):745–752PubMedPubMedCentralCrossRefGoogle Scholar
  32. Koehler KM, Lasky T, Fein SB, Delong SM, Hawkins MA, Rabatsky-Her T (2006) Population-based incidence of infection with selected bacterial enteric pathogens in children younger than five years of age. Pediatr Infect Dis J 25(2):129–134PubMedCrossRefPubMedCentralGoogle Scholar
  33. Krogh A et al (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567–580PubMedCrossRefPubMedCentralGoogle Scholar
  34. Linding R, Jensen LJ, Diella F, Bork P, Gibson TJ, Russell RB (2003) Protein disorder prediction: implications for structural proteomics. Structure 11(11):1453–1459PubMedCrossRefPubMedCentralGoogle Scholar
  35. Lovell SC, Davis IW, Arendall WB, de Bakker PIW, Word JM, Prisant MG, Richardson JS, Richardson DC (2002) Structure validation by C-alpha geometry: phi, psi and -beta deviation. Proteins Struct Funct Genet 50:437–450CrossRefGoogle Scholar
  36. Lupas A, Van Dyke M, Stock J (1991) Predicting coiled coils from protein sequences. Science 252:1162–1164PubMedCrossRefPubMedCentralGoogle Scholar
  37. Matsumoto H, Young GM (2006) Proteomic and functional analysis of the suite of Ysp proteins exported by the Ysa type III secretion system of Yersinia enterocolitica Biovar 1B. Mol Microbiol 59:689–706PubMedCrossRefPubMedCentralGoogle Scholar
  38. Mattei PJ, Faudry E, Job V, Izore T, Attree I, Dessen A (2010) Membrane targeting and pore formation by the type III secretion system translocon. FEBS J 278:414–426PubMedCrossRefPubMedCentralGoogle Scholar
  39. McShan AC, Kaur K, Chatterjee S, Knight KM, De Guzman RN (2016) NMR identification of the binding surfaces involved in the Salmonella and Shigella Type III secretion tip-translocon protein-protein interactions. Proteins 84(8):1097–1107PubMedPubMedCentralCrossRefGoogle Scholar
  40. Mildiner-Earley S, Walker KA, Miller VL (2007) Environmental stimuli affecting expression of the Ysa type three secretion locus. Adv Exp Med Biol 603:211–216PubMedCrossRefGoogle Scholar
  41. Mueller CA, Broz P, Cornelis GR (2008) The type III secretion system tip complex and translocon. Mol Microbiol 68(5):1085–1095PubMedCrossRefGoogle Scholar
  42. Mueller CA, Broz P, Muller SA, Ringler P, Erne-Brand F, Sorg I, Kuhn M, Engel A, Cornelis GR (2005) The V-antigen of Yersinia forms a distinct structure at the tip of injectisome needles. Science 310:674–676PubMedCrossRefGoogle Scholar
  43. Page AL, Parsot C (2002) Chaperones of the type III secretion pathway: jacks of all trades. Mol Microbiol 46:1–11PubMedCrossRefGoogle Scholar
  44. Parsot C, Hamiaux C, Page AL (2003) The various and varying roles of specific chaperones in type III secretion systems. Curr Opin Microbiol 6:7–14PubMedCrossRefGoogle Scholar
  45. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612PubMedCrossRefGoogle Scholar
  46. Pierce BG, Wiehe K, Hwang H, Kim BH, Vreven T, Weng Z (2014) Accelerating protein docking in ZDOCK using an advanced 3D convolution library. Bioinformatics 30(12):1771–1773PubMedPubMedCentralCrossRefGoogle Scholar
  47. Rathinavelan T, Tang C, De Guzman RN (2011) Characterization of the interaction between the Salmonella type III secretion system tip protein SipD and the needle protein PrgI by paramagnetic relaxation enhancement. J Biol Chem 286:4922–4930PubMedCrossRefGoogle Scholar
  48. Roy A, Kucural A, Zhang Y (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nat Protoc 5(4):725–738PubMedPubMedCentralCrossRefGoogle Scholar
  49. The PyMOL Molecular Graphics System, Version 1.3 Schrödinger, LLC. []
  50. Venecia K, Young GM (2005) Environmental regulation and virulence attributes of the Ysa type III secretion system of Yersinia enterocolitica Biovar 1B. Infect Immun 73:5961–5977PubMedPubMedCentralCrossRefGoogle Scholar
  51. Walker KA, Miller VL (2004) Regulation of the Ysa type III secretion system of Yersinia enterocolitica by YsaE/SycB and YsrS/YsrR. J Bacteriol 186:4056–4066PubMedPubMedCentralCrossRefGoogle Scholar
  52. Walker KA, Obrist MW, Mildiner-Earley S, Miller VL (2010) Identification of YsrT and evidence that YsrRST constitute a unique phosphorelay system in Yersinia enterocolitica. J Bacteriol 192(22):5887–5897PubMedPubMedCentralCrossRefGoogle Scholar
  53. Young GM (2007) The Ysa type 3 secretion system of Yersinia enterocolitica Biovar 1B. Adv Exp Med Biol 603:286–297PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Molecular Biology and Biotechnology, Sripat Singh CollegeUniversity of KalyaniMurshidabadIndia
  2. 2.Department of Zoology, Sripat Singh CollegeUniversity of KalyaniMurshidabadIndia

Personalised recommendations