Role of mycobacterium tuberculosis PE and PPE proteins in pathogen-host interactions

This article reviews the discovery, structure, secretion, and role in microbial evolution and immuno-pathogenesis of a group of Mycobacterium tuberculosis acidic glycine rich proteins containing multiple copies of repetitive sequences. The classification of these into PE and PPE proteins is based on the presence of proline-glutamic acid (PE) or proline-proline-glutamic acid (PPE) residues at their N-terminal domains. The structural basis for their interactions in PE-PPE pairs and with mycobacterial protein family secretion systems (ESX or Type VII) is described. We also illustrate the role of these proteins in mycobacterial evolution and immuno-pathogenesis. The emergence of the various lineages and subfamilies of PE and PPE proteins and their ancestral counterparts are described in the context of the interactions of the pathogen with host cells and the elicitation of humoral and cellular immune responses.