Deciphering the molecular mechanism underpinning phage arbitrium communication systems

del Sol, F. G., Penadés, J. R. and Marina, A. (2019) Deciphering the molecular mechanism underpinning phage arbitrium communication systems. Molecular Cell, 74, 59-72.e3. (doi: 10.1016/j.molcel.2019.01.025) (PMID:30745087) (PMCID:PMC6458997)

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Bacillus phages use a communication system, termed “arbitrium,” to coordinate lysis-lysogeny decisions. Arbitrium communication is mediated by the production and secretion of a hexapeptide (AimP) during lytic cycle. Once internalized, AimP reduces the expression of the negative regulator of lysogeny, AimX, by binding to the transcription factor, AimR, promoting lysogeny. We have elucidated the crystal structures of AimR from the Bacillus subtilis SPbeta phage in its apo form, bound to its DNA operator and in complex with AimP. AimR presents intrinsic plasticity, sharing structural features with the RRNPP quorum-sensing family. Remarkably, AimR binds to an unusual operator with a long spacer that interacts nonspecifically with the receptor TPR domain, while the HTH domain canonically recognizes two inverted repeats. AimP stabilizes a compact conformation of AimR that approximates the DNA-recognition helices, preventing AimR binding to the aimX promoter region. Our results establish the molecular basis of the arbitrium communication system.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Penades, Prof Jose R
Creator Roles:
Penades, J. R.Conceptualization, Writing – original draft, Funding acquisition, Resources, Supervision
Authors: del Sol, F. G., Penadés, J. R., and Marina, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Molecular Cell
Publisher:Elsevier (Cell Press)
ISSN (Online):1097-4164
Published Online:07 February 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Molecular Cell 2019 74:59-72.e3
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
660772Molecular biology of the PICIs, a novel and widespread family of mobile genetic elements involved in bacterial virulenceJose R PenadesMedical Research Council (MRC)MR/M003876/1RI INFECTION IMMUNITY & INFLAMMATION
3029710Helper and satellite pathogenicity islands: the discovery of two novel subcellular elements with a huge impact on bacterial pathogenesis and evolutionJose R PenadesBiotechnology and Biological Sciences Research Council (BBSRC)BB/S003835/1III - Bacteriology
727241Understanding bacterial host adaptation to combat infectious diseasesJose R PenadesWellcome Trust (WELLCOTR)201531/Z/16/ZRI INFECTION IMMUNITY & INFLAMMATION
687701DUT-SignalJose R PenadesEuropean Research Council (ERC)670932RI INFECTION IMMUNITY & INFLAMMATION