YspD: A Potential Therapeutic Target for Drug Design to Combat Yersinia enterocolitica Infection
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.
KeywordsType 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.
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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.
- 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
- Carter PB (1975) Pathogenecity of Yersinia enterocolitica for mice. InfectImmun 11:164–170Google Scholar
- Drozdetskiy A, Cole C, Procter J & Barton GJ (2015) JPred4: a protein secondary structure prediction server. Nucleic Acids Res Web Server issueGoogle Scholar
- 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
- Hauser AR (2009) The type III secretion system of Pseudomonas aeruginosa: infection by injection. Nat Reviews 7:654–665Google Scholar
- Ishida T and Kinoshita K (2007) PrDOS. prediction of disordered protein regions from amino acid sequence. Nucleic Acids Res 35:Web Server issueGoogle Scholar
- The PyMOL Molecular Graphics System, Version 1.3 Schrödinger, LLC. [http://www.pymol.org]