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EspG is a key secretion protein involved with the virulence of mycobacterium tuberculosis. The specificity of EspG binding affinity to its specific PE-PPE ligand has many contributing factors. The four different EspG proteins found in mycobacterium tuberculosis have different characteristics that influence binding, where EspG5 binds to the most PE-PPE proteins. Here EspG PE-PPE complex is to be excreted in the ESAT-6 pathway.

EspG5 protein

Function

Through specific binding factors, an EspG binds to its PE-PPE ligand to be secreted through the ESAT pathway. This places

Excretion

EspG PE-PPE excretion is done through the ESX secretion pathway.

Binding

Factors that influence binding of EspG and PE-PPE: Electrostatics: There is a partially negative over all charge on the EspG5 protein.

shape

ligand random coil key catalytic residues

Pocket Residues

Jon

Structural highlights

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Relevance

Publication Abstract from PubMed

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.

Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion.,Ekiert DC, Cox JS Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):14758-63. doi:, 10.1073/pnas.1409345111. Epub 2014 Oct 1. PMID:25275011^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.