PDBsum entry 4w4l

Protein transport

PDB id: 4w4l

Contents

Protein chains

84 a.a.

174 a.a.

297 a.a.

Ligands

EDO

Waters ×76

PDB id:

4w4l

Name:

Protein transport

Title:

Crystal structure of espg5 in complex with pe25 and ppe41 from the esx-5 type vii secretion system of m. Tuberculosis

Structure:

Pe family protein pe25. Chain: a. Engineered: yes. Ppe family protein ppe41. Chain: b. Fragment: unp residues 1-174. Engineered: yes. Espg5. Chain: c.

Source:

Mycobacterium tuberculosis. Organism_taxid: 652616. Strain: erdman. Gene: pe25, erdman_2675, q643_02517. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ppe41, erdman_2674, q643_02516. Gene: erdman_1984, q643_01851.

Resolution:

2.45Å R-factor: 0.203 R-free: 0.230

Authors:

D.C.Ekiert,J.S.Cox

Key ref:

D.C.Ekiert and J.S.Cox (2014). Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion. Proc Natl Acad Sci U S A, 111, 14758-14763. PubMed id: 25275011 DOI: 10.1073/pnas.1409345111

Date:

14-Aug-14 Release date: 01-Oct-14

Protein chain

A0A0H3LBR3  (A0A0H3LBR3_MYCTE) -  PE family protein from Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman)

Seq: 99 a.a.

Struc: 84 a.a.

Protein chain

A0A0H3LBN6  (A0A0H3LBN6_MYCTE) -  PPE family protein from Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman)

Seq: 194 a.a.

Struc: 174 a.a.

Protein chain

A0A0H3LAM1  (A0A0H3LAM1_MYCTE) -  ESX secretion-associated protein EspG from Mycobacterium tuberculosis (strain ATCC 35801 / TMC 107 / Erdman)

Seq: 300 a.a.

Struc: 297 a.a.

DOI no: 10.1073/pnas.1409345111

Proc Natl Acad Sci U S A 111:14758-14763 (2014)

PubMed id: 25275011

Structure of a PE-PPE-EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion.

D.C.Ekiert, J.S.Cox.

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.