Structural elucidation of a novel mechanism for the bacteriophage-based inhibition of the RNA degradosome
- KU Leuven, Belgium
- University of Cambridge, United Kingdom
- Scietific Institute of Public Health, Belgium
- UHasselt, Belgium
Abstract
In all domains of life, the catalysed degradation of RNA facilitates rapid adaptation to changing environmental conditions, while destruction of foreign RNA is an important mechanism to prevent host infection. We have identified a virus-encoded protein termed gp37/Dip, which directly binds and inhibits the RNA degradation machinery of its bacterial host. Encoded by giant phage ΦKZ, this protein associates with two RNA binding sites of the RNase E component of the Pseudomonas aeruginosa RNA degradosome, occluding them from substrates and resulting in effective inhibition of RNA degradation and processing. The 2.2 Å crystal structure reveals that this novel homo-dimeric protein has no identifiable structural homologues. Our biochemical data indicate that acidic patches on the convex outer surface bind RNase E. Through the activity of Dip, ΦKZ has evolved a unique mechanism to down regulate a key metabolic process of its host to allow accumulation of viral RNA in infected cells.
Data availability
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crystal structurePublicly available at the RCSB Protein Data Bank (accession no: 5FT1).
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Mass spectrometry data setPublicly available at the PRIDE Archive (accession no: PXD003285).
Article and author information
Author details
Funding
Fonds Wetenschappelijk Onderzoek (G.0599.11 & Scolarship AV)
- An Van den Bossche
- Pieter-Jan Ceyssens
- Hanne Hendrix
- Rob Lavigne
Agentschap voor Innovatie door Wetenschap en Technologie (SBO 100042)
- An Van den Bossche
- Pieter-Jan Ceyssens
- Rob Lavigne
Onderzoeksraad, KU Leuven (CREA/09/017 & IDO/10/012)
- Abram Aertsen
- Rob Lavigne
Wellcome Trust (scholarship SH, BL)
- Steven W Hardwick
- Ben F Luisi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Gisela Storz, National Institute of Child Health and Human Development, United States
Version history
- Received: April 1, 2016
- Accepted: July 18, 2016
- Accepted Manuscript published: July 22, 2016 (version 1)
- Version of Record published: August 10, 2016 (version 2)
Copyright
© 2016, Van den Bossche et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural elucidation of a novel mechanism for the bacteriophage-based inhibition of the RNA degradosome
eLife 5:e16413.
https://doi.org/10.7554/eLife.16413
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