4W4K

Crystal structure of a PE25-PPE41 heterodimer from a type VII secretion system of M. tuberculosis

Summary for 4W4K

• Entry DOI: 10.2210/pdb4w4k/pdb
• Related: 4W4I 4W4J 4W4L
• Descriptor: PE family protein PE25, PPE family protein PPE41 (3 entities in total)
• Functional Keywords: antigen, virulence factor, protein secretion, adaptor, protein transport
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 4
• Total formula weight: 63685.73

Authors

Ekiert, D.C.,Cox, J.S. (deposition date: 2014-08-14, release date: 2014-10-01, Last modification date: 2023-09-27)

Primary citation

Ekiert, D.C.,Cox, J.S.
Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion.
Proc.Natl.Acad.Sci.USA, 111:14758-14763, 2014

PubMed 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.

PubMed: 25275011
DOI: 10.1073/pnas.1409345111

Experimental method

X-RAY DIFFRACTION (1.95 Å)