The Structural Basis of T4 Phage Lysis Control: DNA as the Signal for Lysis Inhibition.
SAR domain
antiholin
domain swapping
holin
lysis
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
24 07 2020
24 07 2020
Historique:
received:
17
04
2020
revised:
10
06
2020
accepted:
12
06
2020
pubmed:
21
6
2020
medline:
26
1
2021
entrez:
21
6
2020
Statut:
ppublish
Résumé
Optimal phage propagation depends on the regulation of the lysis of the infected host cell. In T4 phage infection, lysis occurs when the holin protein (T) forms lesions in the host membrane. However, the lethal function of T can be blocked by an antiholin (RI) during lysis inhibition (LIN). LIN sets if the infected cell undergoes superinfection, then the lysis is delayed until host/phage ratio becomes more favorable for the release of progeny. It has been thought that a signal derived from the superinfection is required to activate RI. Here we report structures that suggest a radically different model in which RI binds to T irrespective of superinfection, causing it to accumulate in a membrane as heterotetrameric 2RI-2T complex. Moreover, we show the complex binds non-specifically to DNA, suggesting that the gDNA from the superinfecting phage serves as the LIN signal and that stabilization of the complex by DNA binding is what defines LIN. Finally, we show that soluble domain of free RI crystallizes in a domain-swapped homotetramer, which likely works as a sink for RI molecules released from the RI-T complex to ensure efficient lysis. These results constitute the first structural basis and a new model not only for the historic LIN phenomenon but also for the temporal regulation of phage lysis in general.
Identifiants
pubmed: 32562709
pii: S0022-2836(20)30409-5
doi: 10.1016/j.jmb.2020.06.013
pmc: PMC7394242
mid: NIHMS1605785
pii:
doi:
Substances chimiques
DNA, Viral
0
Viral Proteins
0
holin t protein, Enterobacteria phage T4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4623-4636Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM027099
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM136396
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Références
Protein Sci. 2012 Apr;21(4):571-82
pubmed: 22389108
J Struct Biol. 2016 Jan;193(1):1-12
pubmed: 26592709
Elife. 2015 Dec 01;4:
pubmed: 26623517
J Microbiol. 2014 Mar;52(3):243-58
pubmed: 24585055
J Bacteriol. 1948 Feb;55(2):257-76
pubmed: 16561455
Gene. 2001 Mar 7;265(1-2):25-36
pubmed: 11255004
Genetics. 1946 Nov;31(6):620-40
pubmed: 17247224
J Bacteriol. 2014 Nov;196(21):3683-9
pubmed: 25092029
Mol Microbiol. 2001 Aug;41(3):575-83
pubmed: 11532126
Curr Opin Struct Biol. 1996 Jun;6(3):377-85
pubmed: 8804824
Adv Virus Res. 2019;103:33-70
pubmed: 30635077
EMBO J. 1994 Sep 1;13(17):4181-92
pubmed: 8076614
J Bacteriol. 2016 Aug 25;198(18):2448-57
pubmed: 27381920
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
pubmed: 20457744
J Bacteriol. 2014 Jun;196(12):2201-9
pubmed: 24706740
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
Genetics. 1998 Apr;148(4):1539-50
pubmed: 9560373
J Virol. 1971 Dec;8(6):869-86
pubmed: 4950690
J Biol Chem. 2018 Aug 24;293(34):13151-13165
pubmed: 29967063
Elife. 2015 May 29;4:e06980
pubmed: 26023829
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6415-20
pubmed: 15090650
J Struct Biol. 2007 Jan;157(1):38-46
pubmed: 16859925
J Bacteriol. 1965 Oct;90(4):891-4
pubmed: 5321402
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):479-85
pubmed: 20383001
Proteins. 2009 Feb 1;74(2):291-303
pubmed: 18618705
Acta Crystallogr D Biol Crystallogr. 2003 Nov;59(Pt 11):2023-30
pubmed: 14573958
Methods Enzymol. 1997;276:307-26
pubmed: 27754618
Cell Host Microbe. 2019 Feb 13;25(2):219-232
pubmed: 30763536
J Bacteriol. 2005 Oct;187(19):6631-40
pubmed: 16166524
Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3127-31
pubmed: 8159715
J Mol Microbiol Biotechnol. 2002 Jan;4(1):21-36
pubmed: 11763969
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):798-803
pubmed: 21187415
J Mol Biol. 1971 Apr 14;57(1):71-92
pubmed: 4930576
Biochim Biophys Acta. 1968 Jan 29;155(1):98-106
pubmed: 4967316
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
J Bacteriol. 2007 Nov;189(21):7618-25
pubmed: 17693511
Viruses. 2019 Oct 16;11(10):
pubmed: 31623057
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Adv Exp Med Biol. 2012;747:137-52
pubmed: 22949116
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Nat Struct Mol Biol. 2009 Nov;16(11):1192-4
pubmed: 19881499
Structure. 2008 May;16(5):673-83
pubmed: 18462672
J Virol. 1967 Oct;1(5):948-55
pubmed: 4912240