PDBsum entry 4w4l

Protein transport

PDB id: 4w4l

Contents

Protein chains

84 a.a.

174 a.a.

297 a.a.

Ligands

EDO

Waters ×76

References listed in PDB file

Key reference

• Title: Structure of a pe-Ppe-Espg complex from mycobacterium tuberculosis reveals molecular specificity of esx protein secretion.
• Authors: D.C.Ekiert, J.S.Cox.
• Ref.: Proc Natl Acad Sci U S A, 2014, 111, 14758-14763. [DOI no: 10.1073/pnas.1409345111]
• PubMed id: 25275011

Abstract

Nearly 10% of the coding capacity of the Mycobacterium tuberculosis genome is devoted to two highly expanded and enigmatic protein families called PE and PPE, some of which are important virulence/immunogenicity factors and are secreted during infection via a unique alternative secretory system termed "type VII." How PE-PPE proteins function during infection and how they are translocated to the bacterial surface through the five distinct type VII secretion systems [ESAT-6 secretion system (ESX)] of M. tuberculosis is poorly understood. Here, we report the crystal structure of a PE-PPE heterodimer bound to ESX secretion-associated protein G (EspG), which adopts a novel fold. This PE-PPE-EspG complex, along with structures of two additional EspGs, suggests that EspG acts as an adaptor that recognizes specific PE-PPE protein complexes via extensive interactions with PPE domains, and delivers them to ESX machinery for secretion. Surprisingly, secretion of most PE-PPE proteins in M. tuberculosis is likely mediated by EspG from the ESX-5 system, underscoring the importance of ESX-5 in mycobacterial pathogenesis. Moreover, our results indicate that PE-PPE domains function as cis-acting targeting sequences that are read out by EspGs, revealing the molecular specificity for secretion through distinct ESX pathways.