HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies.
HIV-1 Env
MPER broadly neutralizing antibody
bicelle
nanodisc
peptidisc
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
28 04 2020
28 04 2020
Historique:
received:
14
11
2019
revised:
05
03
2020
accepted:
07
04
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
14
5
2021
Statut:
ppublish
Résumé
Structural and functional studies of HIV envelope glycoprotein (Env) as a transmembrane protein have long been complicated by challenges associated with inherent flexibility of the molecule and the membrane-embedded hydrophobic regions. Here, we present approaches for incorporating full-length, wild-type HIV-1 Env, as well as C-terminally truncated and stabilized versions, into lipid assemblies, providing a modular platform for Env structural studies by single particle electron microscopy. We reconstitute a full-length Env clone into a nanodisc, complex it with a membrane-proximal external region (MPER) targeting antibody 10E8, and structurally define the full quaternary epitope of 10E8 consisting of lipid, MPER, and ectodomain contacts. By aligning this and other Env-MPER antibody complex reconstructions with the lipid bilayer, we observe evidence of Env tilting as part of the neutralization mechanism for MPER-targeting antibodies. We also adapt the platform toward vaccine design purposes by introducing stabilizing mutations that allow purification of unliganded Env with a peptidisc scaffold.
Identifiants
pubmed: 32348769
pii: S2211-1247(20)30532-5
doi: 10.1016/j.celrep.2020.107583
pmc: PMC7196886
pii:
doi:
Substances chimiques
HIV Envelope Protein gp41
0
Lipid Bilayers
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
107583Subventions
Organisme : NIAID NIH HHS
ID : R01 AI143563
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI090023
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
Cell Host Microbe. 2019 Jun 12;25(6):873-883.e5
pubmed: 31194940
Nature. 2017 Jul 20;547(7663):360-363
pubmed: 28700571
PLoS Pathog. 2012;8(7):e1002797
pubmed: 22807678
Virology. 2015 May;479-480:498-507
pubmed: 25866377
Nat Commun. 2017 Nov 21;8(1):1655
pubmed: 29162799
J Am Chem Soc. 2018 Jul 5;140(26):8246-8259
pubmed: 29888593
Nat Commun. 2019 Nov 26;10(1):5389
pubmed: 31772165
Retrovirology. 2018 Sep 12;15(1):63
pubmed: 30208933
J Am Chem Soc. 2018 Jan 10;140(1):34-37
pubmed: 29277995
Trends Microbiol. 2019 Oct;27(10):878-891
pubmed: 31262533
Cell Rep. 2018 Jun 12;23(11):3249-3261
pubmed: 29898396
Protein Cell. 2018 Jul;9(7):596-615
pubmed: 29667004
Cell Host Microbe. 2019 Nov 13;26(5):623-637.e8
pubmed: 31653484
Ultramicroscopy. 1999 Jul;77(3-4):153-61
pubmed: 10406132
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Nature. 2014 Nov 6;515(7525):138-42
pubmed: 25186731
J Struct Biol. 2016 Jan;193(1):1-12
pubmed: 26592709
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Methods Enzymol. 2017;594:1-30
pubmed: 28779836
Immunity. 2014 May 15;40(5):669-80
pubmed: 24768348
PLoS Pathog. 2007 May 4;3(5):e63
pubmed: 17480119
AIDS Res Hum Retroviruses. 2001 Dec 10;17(18):1757-65
pubmed: 11788027
Cell Rep. 2017 Dec 5;21(10):2992-3002
pubmed: 29212041
Immunity. 2008 Jan;28(1):52-63
pubmed: 18191596
Immunity. 2019 Jun 18;50(6):1513-1529.e9
pubmed: 31126879
Elife. 2018 Aug 15;7:
pubmed: 30109849
Nature. 2012 Nov 15;491(7424):406-12
pubmed: 23151583
Sci Immunol. 2017 Jan 27;2(7):
pubmed: 28783671
Cell. 2013 Mar 28;153(1):126-38
pubmed: 23540694
Immunol Rev. 2017 Jan;275(1):5-10
pubmed: 28133795
J Struct Biol. 2009 May;166(2):205-13
pubmed: 19374019
J Virol. 2001 Nov;75(22):10892-905
pubmed: 11602729
Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):10112-10117
pubmed: 30224494
Nat Commun. 2018 Sep 12;9(1):3693
pubmed: 30209313
Immunity. 2017 May 16;46(5):792-803.e3
pubmed: 28514686
Cell Rep. 2018 Apr 10;23(2):584-595
pubmed: 29642014
Cell Rep. 2017 Aug 22;20(8):1805-1817
pubmed: 28834745
J Comput Chem. 2008 Aug;29(11):1859-65
pubmed: 18351591
Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):513-8
pubmed: 23267106
Science. 2016 Jul 8;353(6295):172-175
pubmed: 27338706
Cell Microbiol. 2013 Feb;15(2):292-304
pubmed: 23279151
J Mol Biol. 2019 May 31;431(12):2223-2247
pubmed: 31028779
Science. 2016 Mar 4;351(6277):1043-8
pubmed: 26941313
J Am Chem Soc. 2004 Mar 24;126(11):3477-87
pubmed: 15025475
Elife. 2018 Jun 01;7:
pubmed: 29856314
PLoS Pathog. 2019 Jul 15;15(7):e1007920
pubmed: 31306470
Nature. 2008 Sep 4;455(7209):109-13
pubmed: 18668044
Nat Struct Mol Biol. 2015 Jul;22(7):522-31
pubmed: 26098315
Nat Struct Mol Biol. 2016 Jun;23(6):481-6
pubmed: 27273631
PLoS Pathog. 2017 Feb 22;13(2):e1006212
pubmed: 28225819
Immunity. 2017 Nov 21;47(5):990-1003.e9
pubmed: 29166592
Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22556-22566
pubmed: 31624123
Biophys J. 2018 Jul 3;115(1):84-94
pubmed: 29972814
Biotechnol Bioeng. 2018 Apr;115(4):885-899
pubmed: 29150937
Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):E8892-E8899
pubmed: 30185554
Elife. 2018 Nov 09;7:
pubmed: 30412051
J Immunol. 2014 Feb 1;192(3):1100-1106
pubmed: 24391217
Immunity. 2016 Sep 20;45(3):483-496
pubmed: 27617678
Nat Commun. 2019 May 29;10(1):2355
pubmed: 31142746
Immunity. 2019 Mar 19;50(3):677-691.e13
pubmed: 30876875
Retrovirology. 2013 May 24;10:54
pubmed: 23705972
FEBS J. 2017 Apr;284(8):1171-1177
pubmed: 27868386
Nat Commun. 2019 Jan 8;10(1):78
pubmed: 30622256
Nature. 2019 Apr;568(7752):415-419
pubmed: 30971821
Nat Mater. 2017 Apr;16(4):489-496
pubmed: 28024156
Virology. 2003 Sep 30;314(2):636-49
pubmed: 14554091
J Virol. 2017 May 26;91(12):
pubmed: 28381572
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Immunity. 2005 Feb;22(2):163-73
pubmed: 15723805
Immunity. 2016 Jan 19;44(1):21-31
pubmed: 26777395
Science. 2014 Nov 7;346(6210):759-63
pubmed: 25298114
J Exp Med. 2011 Mar 14;208(3):439-54
pubmed: 21357743
Cell Rep. 2018 Feb 13;22(7):1798-1809
pubmed: 29444432
Immunity. 2018 Aug 21;49(2):288-300.e8
pubmed: 30097292
Immunol Rev. 2017 Jan;275(1):21-32
pubmed: 28133813
Nat Struct Mol Biol. 2018 May;25(5):416-424
pubmed: 29728654
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774
Nat Immunol. 2018 Nov;19(11):1179-1188
pubmed: 30333615
J Virol. 2012 Feb;86(3):1820-31
pubmed: 22090143
PLoS Pathog. 2014 Jul 24;10(7):e1004271
pubmed: 25058619
Bioconjug Chem. 2018 Mar 21;29(3):771-775
pubmed: 29485848