One-step sequence and structure-guided optimization of HIV-1 envelope gp140.
Automated
Immunogen
Protein design
Protein stability
Rosetta
Vaccine
Virus
Journal
Current research in structural biology
ISSN: 2665-928X
Titre abrégé: Curr Res Struct Biol
Pays: Netherlands
ID NLM: 101767537
Informations de publication
Date de publication:
2020
2020
Historique:
entrez:
10
3
2021
pubmed:
1
1
2020
medline:
1
1
2020
Statut:
ppublish
Résumé
Stabilization of the metastable envelope glycoprotein (Env) of HIV-1 is hypothesized to improve induction of broadly neutralizing antibodies. We improved the expression yield and stability of the HIV-1 envelope glycoprotein BG505SOSIP.664 gp140 by means of a previously described automated sequence and structure-guided computational thermostabilization approach, PROSS. This combines sequence conservation information with computational assessment of mutant stabilization, thus taking advantage of the extensive natural sequence variation present in HIV-1 Env. PROSS is used to design three gp140 variants with 17-45 mutations relative to the parental construct. One of the designs is experimentally observed to have a fourfold improvement in yield and a 4 °C increment in thermostability. In addition, the designed immunogens have similar antigenicity profiles to the native flexible linker version of wild type, BG505SOSIP.664 gp140 (NFL Wt) to major epitopes targeted by broadly neutralizing antibodies. PROSS eliminates the laborious process of screening many variants for stability and functionality, providing a proof of principle of the method for stabilization and improvement of yield without compromising antigenicity for next generation complex, highly glycosylated vaccine candidates.
Identifiants
pubmed: 33688632
doi: 10.1016/j.crstbi.2020.04.001
pmc: PMC7939140
mid: NIHMS1671504
doi:
Types de publication
Journal Article
Langues
eng
Pagination
45-55Subventions
Organisme : NIAID NIH HHS
ID : R01 AI118366
Pays : United States
Déclaration de conflit d'intérêts
Declaration of Competing Interest None declared
Références
Science. 2013 May 10;340(6133):711-6
pubmed: 23539181
Proc Natl Acad Sci U S A. 2015 Sep 22;112(38):11947-52
pubmed: 26372963
Cell Host Microbe. 2018 Jun 13;23(6):832-844.e6
pubmed: 29902444
Protein Sci. 2018 Jan;27(1):51-61
pubmed: 28795512
Nat Med. 2010 Mar;16(3):319-23
pubmed: 20173752
Science. 2014 Nov 7;346(6210):759-63
pubmed: 25298114
Nat Commun. 2017 Nov 21;8(1):1655
pubmed: 29162799
PLoS Pathog. 2018 May 10;14(5):e1006986
pubmed: 29746590
Immunity. 2015 Dec 15;43(6):1053-63
pubmed: 26682982
Structure. 2010 Sep 8;18(9):1116-26
pubmed: 20826338
Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11275-11284
pubmed: 31110018
Science. 2011 Oct 21;334(6054):373-6
pubmed: 22021856
J Virol. 2014 Sep 1;88(17):9590-604
pubmed: 24920800
Virol J. 2013 Apr 02;10:102
pubmed: 23548077
Cell Rep. 2017 Dec 5;21(10):2992-3002
pubmed: 29212041
PLoS One. 2011;6(6):e20450
pubmed: 21731614
PLoS Pathog. 2013 Feb;9(2):e1003184
pubmed: 23468626
Nat Struct Mol Biol. 2016 Oct;23(10):906-915
pubmed: 27617431
J Virol. 2015 May;89(10):5318-29
pubmed: 25740988
Nature. 2014 Oct 23;514(7523):455-61
pubmed: 25296255
Immunity. 2017 May 16;46(5):792-803.e3
pubmed: 28514686
J Virol. 2014 Sep 1;88(17):9538-52
pubmed: 24965452
Cell Rep. 2017 Aug 22;20(8):1805-1817
pubmed: 28834745
PLoS One. 2015 Mar 30;10(3):e0122443
pubmed: 25822521
Cell Rep. 2018 Apr 10;23(2):584-595
pubmed: 29642014
Cell Rep. 2018 Sep 18;24(12):3324-3338.e5
pubmed: 30232012
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):998-1002
pubmed: 28096331
Cell. 2016 May 5;165(4):813-26
pubmed: 27114034
Science. 2015 Jul 10;349(6244):aac4223
pubmed: 26089353
Nat Struct Mol Biol. 2017 Apr;24(4):370-378
pubmed: 28218750
J Biol Chem. 2018 Feb 2;293(5):1688-1701
pubmed: 29222332
PLoS Pathog. 2016 Aug 03;12(8):e1005767
pubmed: 27487086
PLoS Pathog. 2018 Feb 23;14(2):e1006913
pubmed: 29474444
N Engl J Med. 2009 Dec 3;361(23):2209-20
pubmed: 19843557
J Virol. 2017 Oct 27;91(22):
pubmed: 28878072
Front Immunol. 2018 Jul 17;9:1631
pubmed: 30065725
PLoS Pathog. 2013 Sep;9(9):e1003618
pubmed: 24068931
J Biol Chem. 2013 Apr 5;288(14):9815-25
pubmed: 23430741
Structure. 2014 Jul 8;22(7):974-84
pubmed: 24931470
J Virol. 2013 Apr;87(8):4185-201
pubmed: 23365441
J Biol Chem. 2018 Sep 28;293(39):15002-15020
pubmed: 30093409
J Virol. 2015 Dec 30;90(6):2806-17
pubmed: 26719252
Mol Cell. 2016 Jul 21;63(2):337-346
pubmed: 27425410
Protein Sci. 2019 Jun;28(6):1127-1134
pubmed: 30993730
Immunity. 2016 Sep 20;45(3):483-496
pubmed: 27617678
Nat Commun. 2019 May 29;10(1):2355
pubmed: 31142746
Nat Struct Mol Biol. 2013 Dec;20(12):1352-7
pubmed: 24154805
Methods. 2016 May 1;100:25-34
pubmed: 26931650
Cell Rep. 2016 Nov 22;17(9):2195-2209
pubmed: 27880897
Curr Opin Struct Biol. 2015 Aug;33:161-8
pubmed: 26497286
J Virol. 2015 Jun;89(12):6462-80
pubmed: 25855741
Cell. 2015 Dec 17;163(7):1702-15
pubmed: 26687358
Cell Host Microbe. 2012 Oct 18;12(4):396-407
pubmed: 23084910
Nat Med. 2018 Jun;24(6):857-867
pubmed: 29867235
Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007278
pubmed: 22229123
Immunity. 2018 Aug 21;49(2):288-300.e8
pubmed: 30097292
J Mol Biol. 1994 Jul 15;240(3):188-92
pubmed: 8028003
Cell Rep. 2015 Apr 28;11(4):539-50
pubmed: 25892233
J Virol. 2005 Feb;79(3):1713-23
pubmed: 15650196
AIDS Res Hum Retroviruses. 2017 Aug;33(8):859-868
pubmed: 28314374