Structural insights into Cullin4-RING ubiquitin ligase remodelling by Vpr from simian immunodeficiency viruses.
Amino Acid Sequence
Animals
Cryoelectron Microscopy
Cullin Proteins
/ chemistry
Gene Products, vpr
/ genetics
NEDD8 Protein
/ chemistry
Proteasome Endopeptidase Complex
/ chemistry
Protein Binding
SAM Domain and HD Domain-Containing Protein 1
/ chemistry
Simian Acquired Immunodeficiency Syndrome
/ virology
Simian Immunodeficiency Virus
/ physiology
Ubiquitin-Protein Ligases
/ chemistry
Ubiquitination
Virus Replication
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
19
04
2021
accepted:
02
07
2021
revised:
12
08
2021
pubmed:
3
8
2021
medline:
1
12
2021
entrez:
2
8
2021
Statut:
epublish
Résumé
Viruses have evolved means to manipulate the host's ubiquitin-proteasome system, in order to down-regulate antiviral host factors. The Vpx/Vpr family of lentiviral accessory proteins usurp the substrate receptor DCAF1 of host Cullin4-RING ligases (CRL4), a family of modular ubiquitin ligases involved in DNA replication, DNA repair and cell cycle regulation. CRL4DCAF1 specificity modulation by Vpx and Vpr from certain simian immunodeficiency viruses (SIV) leads to recruitment, poly-ubiquitylation and subsequent proteasomal degradation of the host restriction factor SAMHD1, resulting in enhanced virus replication in differentiated cells. To unravel the mechanism of SIV Vpr-induced SAMHD1 ubiquitylation, we conducted integrative biochemical and structural analyses of the Vpr protein from SIVs infecting Cercopithecus cephus (SIVmus). X-ray crystallography reveals commonalities between SIVmus Vpr and other members of the Vpx/Vpr family with regard to DCAF1 interaction, while cryo-electron microscopy and cross-linking mass spectrometry highlight a divergent molecular mechanism of SAMHD1 recruitment. In addition, these studies demonstrate how SIVmus Vpr exploits the dynamic architecture of the multi-subunit CRL4DCAF1 assembly to optimise SAMHD1 ubiquitylation. Together, the present work provides detailed molecular insight into variability and species-specificity of the evolutionary arms race between host SAMHD1 restriction and lentiviral counteraction through Vpx/Vpr proteins.
Identifiants
pubmed: 34339457
doi: 10.1371/journal.ppat.1009775
pii: PPATHOGENS-D-21-00839
pmc: PMC8360603
doi:
Substances chimiques
Cullin Proteins
0
Gene Products, vpr
0
NEDD8 Protein
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
SAM Domain and HD Domain-Containing Protein 1
EC 3.1.5.-
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009775Subventions
Organisme : Wellcome Trust
ID : 103139
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203149
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108014/Z/15/Z
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21136-41
pubmed: 24324150
J Virol. 2005 Sep;79(17):10978-87
pubmed: 16103149
Curr Protoc Bioinformatics. 2015 Dec 17;52:5.8.1-5.8.15
pubmed: 26678386
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
Cell Rep. 2019 Apr 30;27(5):1579-1596.e7
pubmed: 31042482
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):22-5
pubmed: 20057045
Anal Chem. 2017 Apr 4;89(7):3829-3833
pubmed: 28267312
Science. 2012 May 25;336(6084):1030-3
pubmed: 22628654
Proc Natl Acad Sci U S A. 2014 May 6;111(18):E1843-51
pubmed: 24753578
Cells. 2019 Oct 24;8(11):
pubmed: 31652959
Sci STKE. 2006 May 16;2006(335):pe21
pubmed: 16705129
J Virol. 2002 Mar;76(5):2159-67
pubmed: 11836393
Curr Protoc Bioinformatics. 2016 Jun 20;54:5.6.1-5.6.37
pubmed: 27322406
Cell. 2014 Jan 16;156(1-2):134-45
pubmed: 24412650
Gene. 2015 Nov 15;573(1):33-45
pubmed: 26344709
Nat Biotechnol. 2008 Oct;26(10):1187-92
pubmed: 18806783
Nature. 2016 Mar 17;531(7594):386-9
pubmed: 26983541
Cell. 2011 Nov 23;147(5):1024-39
pubmed: 22118460
Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8949-54
pubmed: 10430876
Cell. 2006 Jan 13;124(1):105-17
pubmed: 16413485
Curr Opin Virol. 2012 Dec;2(6):755-63
pubmed: 23062609
Nature. 2014 Aug 7;512(7512):49-53
pubmed: 25043012
Nat Rev Mol Cell Biol. 2015 Jan;16(1):30-44
pubmed: 25531226
Biomolecules. 2014 Oct 13;4(4):897-930
pubmed: 25314029
Nat Rev Immunol. 2012 Oct;12(10):687-95
pubmed: 22976433
Proc Natl Acad Sci U S A. 2014 Oct 14;111(41):E4305-14
pubmed: 25267621
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
J Virol. 2012 May;86(10):5497-507
pubmed: 22379088
Elife. 2018 Mar 07;7:
pubmed: 29513216
J Biol Chem. 2014 Nov 21;289(47):32617-27
pubmed: 25288794
Mol Cell. 2007 Jun 22;26(6):775-80
pubmed: 17588513
Mol Cell. 2018 Jun 7;70(5):961-970.e5
pubmed: 29883611
Sci Rep. 2018 May 23;8(1):8067
pubmed: 29795228
EMBO J. 2013 Sep 11;32(18):2454-62
pubmed: 23872947
Nat Microbiol. 2018 Dec;3(12):1354-1361
pubmed: 30297740
J Vis Exp. 2017 May 16;(123):
pubmed: 28570515
Clin Infect Dis. 2019 Jan 7;68(2):177-187
pubmed: 30052811
Cell Rep. 2016 Sep 13;16(11):2846-2854
pubmed: 27626656
Nat Microbiol. 2018 Aug;3(8):891-897
pubmed: 29891865
Proc Natl Acad Sci U S A. 2016 May 10;113(19):5311-6
pubmed: 27114546
Nat Rev Drug Discov. 2019 Dec;18(12):949-963
pubmed: 31666732
Retrovirology. 2014 Apr 08;11:29
pubmed: 24712655
Int J Mol Sci. 2019 Apr 02;20(7):
pubmed: 30986950
Front Microbiol. 2011 Jul 28;2:161
pubmed: 21847386
J Leukoc Biol. 2015 Jul;98(1):5-14
pubmed: 25646359
Nature. 2006 Oct 5;443(7111):590-3
pubmed: 16964240
J Virol. 2015 Jan;89(1):230-40
pubmed: 25320300
Nat Struct Mol Biol. 2018 Nov;25(11):1000-1008
pubmed: 30374081
Cell Host Microbe. 2019 Jan 9;25(1):27-38
pubmed: 30629915
Annu Rev Genet. 2012;46:677-700
pubmed: 23145935
Curr Opin Struct Biol. 2010 Dec;20(6):714-21
pubmed: 20880695
J Biol Chem. 2013 Jun 28;288(26):19116-26
pubmed: 23677995
J Biol Chem. 2012 Jun 22;287(26):21570-4
pubmed: 22589553
Annu Rev Biochem. 2017 Jun 20;86:129-157
pubmed: 28375744
J Biol Chem. 2015 Jul 10;290(28):17380-9
pubmed: 26032416
Nature. 2014 Jan 9;505(7482):234-8
pubmed: 24336198
Cell Host Microbe. 2009 Jun 18;5(6):559-70
pubmed: 19527883
Front Microbiol. 2014 Mar 31;5:127
pubmed: 24744753
Retrovirology. 2012 Dec 11;9:105
pubmed: 23231760
Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841
pubmed: 22229120
Nat Med. 2012 Nov;18(11):1682-7
pubmed: 22972397
PLoS Pathog. 2015 Sep 01;11(9):e1005143
pubmed: 26325027
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Bioinformatics. 2015 Oct 1;31(19):3222-4
pubmed: 26026169
Adv Exp Med Biol. 2020;1217:61-78
pubmed: 31898222
Nucleic Acids Res. 2019 Jul 2;47(W1):W636-W641
pubmed: 30976793
Elife. 2018 Nov 09;7:
pubmed: 30412051
J Biol Chem. 2015 Jul 17;290(29):17935-17945
pubmed: 26045556
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Nature. 2011 May 25;474(7353):654-7
pubmed: 21613998
Curr Opin Chem Biol. 2020 Jun;56:35-41
pubmed: 31901786
PLoS Pathog. 2011 Jun;7(6):e1002069
pubmed: 21698215
PLoS Pathog. 2015 Oct 02;11(10):e1005194
pubmed: 26431200
Nat Struct Mol Biol. 2016 Oct;23(10):933-940
pubmed: 27571178
Nat Cell Biol. 2009 May;11(5):527-34
pubmed: 19404332
Cell. 2008 Dec 26;135(7):1213-23
pubmed: 19109893
Viruses. 2021 Jan 17;13(1):
pubmed: 33477360
PLoS Pathog. 2015 May 21;11(5):e1004928
pubmed: 25996507
Nat Immunol. 2012 Feb 12;13(3):223-228
pubmed: 22327569
Drug Discov Today. 2019 May;24(5):1139-1147
pubmed: 30885676
Nat Protoc. 2006;1(6):2856-60
pubmed: 17406544
J Biol Chem. 2015 May 22;290(21):13279-92
pubmed: 25847232
Methods Mol Biol. 1999;112:531-52
pubmed: 10027275
J Mol Graph Model. 2002 Dec;21(3):181-3
pubmed: 12463636
Nature. 2020 Feb;578(7795):461-466
pubmed: 32051583
Mol Syst Biol. 2019 Sep;15(9):e8994
pubmed: 31556486
J Virol. 1996 Apr;70(4):2516-24
pubmed: 8642681
Nat Commun. 2013;4:2722
pubmed: 24217394
J Struct Biol. 2003 Jun;142(3):334-47
pubmed: 12781660
J Struct Biol. 2005 Jul;151(1):41-60
pubmed: 15890530
Acta Crystallogr D Biol Crystallogr. 2015 Mar;71(Pt 3):516-24
pubmed: 25760601
J Struct Biol. 2000 Oct;132(1):33-45
pubmed: 11121305
Nat Struct Mol Biol. 2013 Nov;20(11):1304-9
pubmed: 24141705
Cold Spring Harb Perspect Med. 2012 May;2(5):a006940
pubmed: 22553496
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Nucleic Acids Res. 2003 Jan 15;31(2):E6-6
pubmed: 12527795
Lancet. 2008 Jul 26;372(9635):293-9
pubmed: 18657708
Nature. 2011 Jun 29;474(7353):658-61
pubmed: 21720370
Viruses. 2017 Oct 31;9(11):
pubmed: 29088112
Int J Mol Sci. 2017 Jan 10;18(1):
pubmed: 28075409
Nature. 2011 Nov 06;480(7377):379-82
pubmed: 22056990
PLoS Pathog. 2013;9(7):e1003496
pubmed: 23874202
J Mol Biol. 2017 Feb 3;429(3):399-407
pubmed: 27939290
Science. 2014 Jun 20;344(6190):1401-5
pubmed: 24948736
J Biol Chem. 2011 Dec 23;286(51):43596-43600
pubmed: 22069334
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Nat Med. 1997 Apr;3(4):389-94
pubmed: 9095171
J Virol. 1997 Jun;71(6):4331-8
pubmed: 9151821
J Biol Chem. 2016 Aug 12;291(33):16936-16947
pubmed: 27354282
Biochem Soc Trans. 2019 Aug 30;47(4):1013-1027
pubmed: 31296733
Anal Chem. 2003 Feb 1;75(3):663-70
pubmed: 12585499
Cell Host Microbe. 2012 Feb 16;11(2):194-204
pubmed: 22284954
Cell. 2008 Sep 19;134(6):995-1006
pubmed: 18805092
Anal Chem. 2017 May 16;89(10):5311-5318
pubmed: 28402676
J Biol Chem. 2013 Apr 12;288(15):10406-17
pubmed: 23426366
J Mol Biol. 2003 Mar 14;327(1):215-27
pubmed: 12614620
Cell Discov. 2018 Dec 11;4:67
pubmed: 30564455
Nat Microbiol. 2019 Dec;4(12):2552-2564
pubmed: 31659299
Cell Host Microbe. 2015 Apr 8;17(4):489-99
pubmed: 25856754
Trends Biochem Sci. 2018 Mar;43(3):157-169
pubmed: 29395654