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Intrinsically Disordered Regions in PE/PPE Protein Family of Mycobacterium tuberculosis: Moonlighting Function

  • Farha Naz
  • Javeed Ahmad
  • Mohd Shariq
  • Mohd Arish
  • Javaid A. Sheikh
  • Seyed E. Hasnain
  • Nasreen Z. EhteshamEmail author
Chapter

Abstract

Mycobacterium tuberculosis, the causative agent of tuberculosis, has the distinction of harboring an unusual set of plentiful antigens that are highly homologous. The abundance of similar proteins like PE/PPE that are restricted to pathogenic mycobacterium species implies their important role in either homeostasis or helping to adapt to the intracellular niche which is one of the major life cycle stages in pathogenesis of this bacterium. In spite of the various important functions delineated for this family, it is always challenging to study this extremely homologous family of proteins due to difficulties associated with expression and purification. Phylogenetic studies suggest that pe/ppe genes coevolved with esx loci, which encodes proteins that form secretion systems for the export of PE/PPE proteins. Despite the biochemical and immunological characterization of various PE/PPE proteins, there is dearth of structural data for PE/PPE complex. The structural details and thus the structure-function relation are essential to understand the utility of homologous protein repertoire in pathogenesis. Moreover, the atomic detail could unravel the novel targets to curb this obnoxious pathogen. This chapter will present in detail the structural organization as well as the disorder content of the PE/PPE family. This structural enigma of being highly homologous along with having highest disorder content will be explained with possible functional significance. The available crystal structure and predictions on the basis of those accompanied with functional aspect of their role in cell death pathways are also detailed herein.

Keywords

Structural disorder PE/PPE proteins Crystal structure Programmed cell death Apoptosis Necrosis 

Abbreviations

(M.tb)

Mycobacterium tuberculosis

LCR

Low complexity region

PCD

Programmed cell death

PE

Proline-glutamic acid

PPE

Proline-proline-glutamic acid

RMSD

Root-mean-square deviation

TB

Tuberculosis

TLR

Toll-like receptor

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Farha Naz
    • 1
  • Javeed Ahmad
    • 1
  • Mohd Shariq
    • 1
  • Mohd Arish
    • 2
  • Javaid A. Sheikh
    • 3
  • Seyed E. Hasnain
    • 2
    • 4
  • Nasreen Z. Ehtesham
    • 1
    Email author
  1. 1.Inflammation Biology and Cell Signaling LaboratoryICMR-National Institute of Pathology, Safdarjung Hospital CampusNew DelhiIndia
  2. 2.JH Institute of Molecular Medicine, Jamia HamdardNew DelhiIndia
  3. 3.Department of BiotechnologySchool of Chemical and Life Sciences, Jamia HamdardNew DelhiIndia
  4. 4.Dr Reddy’s Institute of Life SciencesUniversity of Hyderabad CampusHyderabadIndia

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