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

DOI: 10.1038/s41467-020-16681-z DOI Help

Authors: Amit Meir (Institute of Structural and Molecular Biology, Birkbeck and UCL; Yale University) , Kevin Mace (Institute of Structural and Molecular Biology, Birkbeck and UCL) , Natalya Lukoyanova (Institute of Structural and Molecular Biology, Birkbeck and UCL) , David Chetrit (Yale University) , Manuela K. Hospenthal (ETH Z├╝rich; Institute of Structural and Molecular Biology, Birkbeck and UCL) , Adam Redzej (Institute of Structural and Molecular Biology, Birkbeck and UCL) , Craig Roy (Yale University) , Gabriel Waksman (Institute of Structural and Molecular Biology, Birkbeck and UCL)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: June 2020
Diamond Proposal Number(s): 14704

Open Access Open Access

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.

Journal Keywords: Bacterial secretion; Bacterial structural biology; Bacteriology; Structural biology

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios IV-Titan Krios IV at Diamond

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s41467-020-16681-z.pdf

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