4W4K: Crystal Structure Of A Pe25-ppe41 Heterodimer From A Type Vii Secretion System Of M. Tuberculosis

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.
PDB ID: 4W4KDownload
MMDB ID: 123980
PDB Deposition Date: 2014/8/14
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 1.95  Å
Source Organism:
Similar Structures:
Biological Unit for 4W4K: dimeric; determined by author and by software (PISA)
Molecular Components in 4W4K
Label Count Molecule
Proteins (2 molecules)
PE Family Protein Pe25
Molecule annotation
PPE Family Protein Ppe41
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB