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TitleStructure of EspB from the ESX-1 type VII secretion system and insights into its export mechanism.
Journal, issue, pagesStructure, Vol. 23, Issue 3, Page 571-583, Year 2015
Publish dateMar 3, 2015
AuthorsMatthew Solomonson / Dheva Setiaputra / Karl A T Makepeace / Emilie Lameignere / Evgeniy V Petrotchenko / Deborah G Conrady / Julien R Bergeron / Marija Vuckovic / Frank DiMaio / Christoph H Borchers / Calvin K Yip / Natalie C J Strynadka /
PubMed AbstractMycobacterium tuberculosis (Mtb) uses the ESX-1 type VII secretion system to export virulence proteins across its lipid-rich cell wall, which helps permeabilize the host's macrophage phagosomal ...Mycobacterium tuberculosis (Mtb) uses the ESX-1 type VII secretion system to export virulence proteins across its lipid-rich cell wall, which helps permeabilize the host's macrophage phagosomal membrane, facilitating the escape and cell-to-cell spread of Mtb. ESX-1 membranolytic activity depends on a set of specialized secreted Esp proteins, the structure and specific roles of which are not currently understood. Here, we report the X-ray and electron microscopic structures of the ESX-1-secreted EspB. We demonstrate that EspB adopts a PE/PPE-like fold that mediates oligomerization with apparent heptameric symmetry, generating a barrel-shaped structure with a central pore that we propose contributes to the macrophage killing functions of EspB. Our structural data also reveal unexpected direct interactions between the EspB bipartite secretion signal sequence elements that form a unified aromatic surface. These findings provide insight into how specialized proteins encoded within the ESX-1 locus are targeted for secretion, and for the first time indicate an oligomerization-dependent role for Esp virulence factors.
External linksStructure / PubMed:25684576
MethodsEM (single particle) / X-ray diffraction
Resolution2.415 - 30.0 Å
Structure data

EMDB-6120: Structure of a mycobacterial protein
PDB-3j83: Heptameric EspB Rosetta model guided by EM density
Method: EM (single particle) / Resolution: 30.0 Å

PDB-4wj1:
Crystal structure of EspB from the ESX-1 type VII secretion system
Method: X-RAY DIFFRACTION / Resolution: 2.415 Å

PDB-4wj2:
Mycobacterial protein
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • Mycobacterium tuberculosis (bacteria)
  • mycobacterium tuberculosis h37rv (bacteria)
  • mycobacterium smegmatis (bacteria)
KeywordsPROTEIN BINDING / PROTEIN TRANSPORT / Mycobacterial protein / UNKNOWN FUNCTION

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