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

  • Debjani Mandal
  • Debabrata Mandal
  • Abhishek BasuEmail author
Article

Abstract

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.

Keywords

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

Notes

Acknowledgement

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)

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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

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