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

Meir, A., Macé, K., Lukoyanova, N., Chetrit, D., Hospenthal, M. K., Redzej, A., Roy, C. and Waksman, G. (2020) Mechanism of effector capture and delivery by the type IV secretion system from Legionella pneumophila. Nature Communications, 11, 2864. (doi: 10.1038/s41467-020-16681-z) (PMID:32513920) (PMCID:PMC7280309)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Meir Ben Efraim, Dr Amit
• Authors: Meir, A., Macé, K., Lukoyanova, N., Chetrit, D., Hospenthal, M. K., Redzej, A., Roy, C., and Waksman, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Nature Communications 11: 2864
• Publisher Policy: Reproduced under a Creative Commons License
• Data DOI: 10.2210/pdb6SZ9/pdb