TY - JOUR
T1 - Structure of EspB, a secreted substrate of the ESX-1 secretion system of Mycobacterium tuberculosis
AU - Korotkova, Natalia
AU - Piton, Jérémie
AU - Wagner, Jonathan M.
AU - Boy-Röttger, Stefanie
AU - Japaridze, Aleksandre
AU - Evans, Timothy J.
AU - Cole, Stewart T.
AU - Pojer, Florence
AU - Korotkov, Konstantin V.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - Mycobacterium tuberculosis secretes multiple virulence factors during infection via the general Sec and Tat pathways, and via specialized ESX secretion systems, also referred to as type VII secretion systems. The ESX-1 secretion system is an important virulence determinant because deletion of ESX-1 leads to attenuation of M. tuberculosis. ESX-1 secreted protein B (EspB) contains putative PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains, and a C-terminal domain, which is processed by MycP1 protease during secretion. We determined the crystal structure of PE-PPE domains of EspB, which represents an all-helical, elongated molecule closely resembling the structure of the PE25-PPE41 heterodimer despite limited sequence similarity. Also, we determined the structure of full-length EspB, which does not have interpretable electron density for the C-terminal domain confirming that it is largely disordered. Comparative analysis of EspB in cell lysate and culture filtrates of M. tuberculosis revealed that mature secreted EspB forms oligomers. Electron microscopy analysis showed that the N-terminal fragment of EspB forms donut-shaped particles. These data provide a rationale for the future investigation of EspB's role in M. tuberculosis pathogenesis.
AB - Mycobacterium tuberculosis secretes multiple virulence factors during infection via the general Sec and Tat pathways, and via specialized ESX secretion systems, also referred to as type VII secretion systems. The ESX-1 secretion system is an important virulence determinant because deletion of ESX-1 leads to attenuation of M. tuberculosis. ESX-1 secreted protein B (EspB) contains putative PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains, and a C-terminal domain, which is processed by MycP1 protease during secretion. We determined the crystal structure of PE-PPE domains of EspB, which represents an all-helical, elongated molecule closely resembling the structure of the PE25-PPE41 heterodimer despite limited sequence similarity. Also, we determined the structure of full-length EspB, which does not have interpretable electron density for the C-terminal domain confirming that it is largely disordered. Comparative analysis of EspB in cell lysate and culture filtrates of M. tuberculosis revealed that mature secreted EspB forms oligomers. Electron microscopy analysis showed that the N-terminal fragment of EspB forms donut-shaped particles. These data provide a rationale for the future investigation of EspB's role in M. tuberculosis pathogenesis.
KW - ESX
KW - PE domain
KW - PPE domain
KW - Type VII secretion system
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U2 - 10.1016/j.jsb.2015.06.003
DO - 10.1016/j.jsb.2015.06.003
M3 - Article
C2 - 26051906
AN - SCOPUS:84937817692
SN - 1047-8477
VL - 191
SP - 236
EP - 244
JO - Journal of Structural Biology
JF - Journal of Structural Biology
IS - 2
ER -