A complex between the Zika virion and the Fab of a broadly cross-reactive neutralizing monoclonal antibody revealed by cryo-EM and single particle analysis at 4.1 Å resolution.
Cryo-electron microscopy
Fab
Neutralizing antibody
Zika virus
Journal
Journal of structural biology: X
ISSN: 2590-1524
Titre abrégé: J Struct Biol X
Pays: United States
ID NLM: 101761384
Informations de publication
Date de publication:
2020
2020
Historique:
received:
24
02
2020
revised:
10
06
2020
accepted:
11
06
2020
entrez:
11
7
2020
pubmed:
11
7
2020
medline:
11
7
2020
Statut:
epublish
Résumé
Zika virus (ZIKV) recently emerged as a major public health concern because it can cause fetal microcephaly and neurological disease such as the Guillain-Barré syndrome. A particularly potent class of broadly neutralizing antibodies (nAbs) targets a quaternary epitope located at the interface of two envelope proteins monomers, exposed at the surface of the mature virion. This "E-dimer-dependent epitope" (EDE), comprises the fusion loop of one monomer at the tip of domain II of E and a portion of the domains I and III of the adjacent monomer. Since this epitope largely overlaps with the binding site of the precursor membrane protein (prM) during Zika virion maturation, its molecular surface is evolutionary conserved in flaviviruses such as Dengue and Zika viruses, and can elicit antibodies that broadly neutralize various ZIKV strains. Here, we present a cryo-EM reconstruction at 4.1 Å resolution of the virion bound to the antigen binding fragment (Fab) of an antibody that targets this mutationally-constrained quaternary epitope. The Fab incompletely covers the surface of the virion as it does not bind next to its 5-fold icosahedral axes. The structure reveals details of the binding mode of this potent neutralizing class of antibodies and can inform the design of immunogens and vaccines targeting this conserved epitope.
Identifiants
pubmed: 32647830
doi: 10.1016/j.yjsbx.2020.100028
pii: S2590-1524(20)30010-6
pii: 100028
pmc: PMC7337043
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100028Informations de copyright
© 2020 The Authors.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Nat Immunol. 2017 Nov;18(11):1261-1269
pubmed: 28945244
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Lancet. 2017 Nov 4;390(10107):2099-2109
pubmed: 28647173
Science. 2016 Apr 22;352(6284):467-70
pubmed: 27033547
Proc Natl Acad Sci U S A. 2012 May 8;109(19):7439-44
pubmed: 22499787
Trends Biochem Sci. 2017 Jun;42(6):443-456
pubmed: 28318966
EMBO Mol Med. 2014 Mar;6(3):358-71
pubmed: 24421336
Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):E1555-64
pubmed: 23569282
J Gen Virol. 2012 Jan;93(Pt 1):72-82
pubmed: 21957126
Nat Methods. 2014 Jan;11(1):63-5
pubmed: 24213166
Nature. 2016 Aug 4;536(7614):48-53
pubmed: 27338953
J Struct Biol. 2007 Jan;157(1):38-46
pubmed: 16859925
PLoS One. 2011 Jan 11;6(1):e16059
pubmed: 21264311
Ann Acad Med Singapore. 2006 Nov;35(11):783-9
pubmed: 17160194
Nature. 2016 Apr 19;533(7603):425-8
pubmed: 27093288
Nat Commun. 2016 Nov 24;7:13679
pubmed: 27882950
Sci Transl Med. 2012 Jun 20;4(139):139ra83
pubmed: 22723463
EMBO Rep. 2003 Jul;4(7):723-8
pubmed: 12783086
Nature. 2015 Apr 2;520(7545):109-13
pubmed: 25581790
Am J Stem Cells. 2017 Jul 25;6(2):13-22
pubmed: 28804687
Sci Transl Med. 2016 Dec 14;8(369):369ra179
pubmed: 27974667
J Virol. 2010 Sep;84(18):9227-39
pubmed: 20592088
Int J Mol Sci. 2017 Dec 25;19(1):
pubmed: 29295568
Nature. 2005 Sep 29;437(7059):764-9
pubmed: 16193056
Nucleic Acids Res. 2013 Jan;41(Database issue):D824-7
pubmed: 23203891
Nat Immunol. 2015 Feb;16(2):170-177
pubmed: 25501631
PLoS Pathog. 2008 Feb 8;4(2):e17
pubmed: 18266465
PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2636
pubmed: 24421913
Emerg Infect Dis. 2008 Aug;14(8):1232-9
pubmed: 18680646
Emerg Microbes Infect. 2017 Mar 22;6(3):e13
pubmed: 28325921
Cell. 2017 May 04;169(4):597-609.e11
pubmed: 28475892
Cell. 2015 Jul 30;162(3):493-504
pubmed: 26189681
Nat Immunol. 2016 Sep;17(9):1102-8
pubmed: 27339099
J Virol. 2006 Jul;80(14):6982-92
pubmed: 16809304
PLoS One. 2014 Jun 02;9(6):e98785
pubmed: 24886790
Nat Commun. 2015 Feb 20;6:6341
pubmed: 25698059
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Nucleic Acids Res. 2017 Jul 3;45(W1):W550-W553
pubmed: 28431173
Nat Methods. 2013 Jun;10(6):584-90
pubmed: 23644547
mBio. 2013 Nov 19;4(6):e00873-13
pubmed: 24255124
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Nature. 2004 Jan 22;427(6972):313-9
pubmed: 14737159
Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1591-1596
pubmed: 30642974
Science. 2015 Jul 3;349(6243):88-91
pubmed: 26138979
Cell Host Microbe. 2018 May 9;23(5):618-627.e6
pubmed: 29746833
J Virol. 2007 Nov;81(21):11828-39
pubmed: 17715236
Cell. 2006 Feb 10;124(3):485-93
pubmed: 16469696
J Exp Med. 2003 Apr 7;197(7):823-9
pubmed: 12682107
Cell. 2016 Aug 11;166(4):1016-1027
pubmed: 27475895
Proc Natl Acad Sci U S A. 2007 May 29;104(22):9422-7
pubmed: 17517625
Viruses. 2018 May 02;10(5):
pubmed: 29724036
Nat Rev Immunol. 2015 Dec;15(12):745-59
pubmed: 26603900
J Struct Biol. 2003 Jun;142(3):334-47
pubmed: 12781660
Science. 2016 Aug 19;353(6301):823-6
pubmed: 27417494
J Neurovirol. 2014 Dec;20(6):539-60
pubmed: 25287260
Emerg Infect Dis. 2015 Oct;21(10):1887
pubmed: 26403318
J Chem Inf Model. 2011 Oct 24;51(10):2778-86
pubmed: 21919503
Microbes Infect. 2011 Jan;13(1):1-9
pubmed: 20869460
Cell Rep. 2016 Aug 9;16(6):1485-1491
pubmed: 27481466
Cell Host Microbe. 2016 May 11;19(5):696-704
pubmed: 27158114
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
J Struct Biol. 2012 Dec;180(3):519-30
pubmed: 23000701