Mechanism of effector capture and delivery by the type IV secretion system from Legionella pneumophila.

Nature Communications
Amit MeirGabriel Waksman

Abstract

Legionella pneumophila is a bacterial pathogen that utilises a Type IV secretion (T4S) system to inject effector proteins into human macrophages. Essential to the recruitment and delivery of effectors to the T4S machinery is the membrane-embedded T4 coupling complex (T4CC). Here, we purify an intact T4CC from the Legionella membrane. It contains the DotL ATPase, the DotM and DotN proteins, the chaperone module IcmSW, and two previously uncharacterised proteins, DotY and DotZ. The atomic resolution structure reveals a DotLMNYZ hetero-pentameric core from which the flexible IcmSW module protrudes. Six of these hetero-pentameric complexes may assemble into a 1.6-MDa hexameric nanomachine, forming an inner membrane channel for effectors to pass through. Analysis of multiple cryo EM maps, further modelling and mutagenesis provide working models for the mechanism for binding and delivery of two essential classes of Legionella effectors, depending on IcmSW or DotM, respectively.

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Citations

Dec 17, 2020·Molecular Microbiology·Tiago R D CostaPeter J Christie
Mar 3, 2021·The FEBS Journal·Andrey GrishinMiroslaw Cygler
Apr 13, 2021·Virulence·Deepika Chauhan, Stephanie R Shames
Mar 29, 2021·Cellular Microbiology·Samuel SteinerCraig R Roy
Apr 30, 2021·Microbiology and Molecular Biology Reviews : MMBR·Steven L FoleyJing Han

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Methods Mentioned

BETA
pull-down
PCR
PISA
ELISA

Software Mentioned

MOLPROBITY
RELION
CRYOSPARC
GraphPad Prism
CHIMERA
IcmSW
CHIMERAX
CTFFIND
MOTIONCOR2
PSIPRED

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