Cryo-EM structure of eastern equine encephalitis virus in complex with heparan sulfate analogues.
Animals
Antiviral Agents
/ pharmacology
Binding Sites
/ drug effects
Cell Line
Chondroitin Sulfates
/ pharmacology
Cryoelectron Microscopy
Drug Design
Encephalitis Virus, Eastern Equine
/ metabolism
Encephalomyelitis, Equine
/ drug therapy
Heparan Sulfate Proteoglycans
/ analogs & derivatives
Heparin
/ metabolism
Humans
Mesocricetus
Molecular Structure
Structure-Activity Relationship
Viral Envelope Proteins
/ metabolism
Virus Attachment
/ drug effects
alphavirus
cryoelectron microscopy
heparan sulfate proteoglycan
infection
structure
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
21 04 2020
21 04 2020
Historique:
pubmed:
5
4
2020
medline:
28
7
2020
entrez:
5
4
2020
Statut:
ppublish
Résumé
Eastern equine encephalitis virus (EEEV), a mosquito-borne icosahedral alphavirus found mainly in North America, causes human and equine neurotropic infections. EEEV neurovirulence is influenced by the interaction of the viral envelope protein E2 with heparan sulfate (HS) proteoglycans from the host's plasma membrane during virus entry. Here, we present a 5.8-Å cryoelectron microscopy (cryo-EM) structure of EEEV complexed with the HS analog heparin. "Peripheral" HS binding sites were found to be associated with the base of each of the E2 glycoproteins that form the 60 quasi-threefold spikes (q3) and the 20 sites associated with the icosahedral threefold axes (i3). In addition, there is one HS site at the vertex of each q3 and i3 spike (the "axial" sites). Both the axial and peripheral sites are surrounded by basic residues, suggesting an electrostatic mechanism for HS binding. These residues are highly conserved among EEEV strains, and therefore a change in these residues might be linked to EEEV neurovirulence.
Identifiants
pubmed: 32245806
pii: 1910670117
doi: 10.1073/pnas.1910670117
pmc: PMC7183182
doi:
Substances chimiques
Antiviral Agents
0
Heparan Sulfate Proteoglycans
0
Viral Envelope Proteins
0
glycoprotein E2, equine encephalitis virus
0
Heparin
9005-49-6
Chondroitin Sulfates
9007-28-7
Banques de données
PDB
['6ODF']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
8890-8899Subventions
Organisme : NIAID NIH HHS
ID : R01 AI095366
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095436
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Nature. 2018 May;557(7706):570-574
pubmed: 29769725
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
J Biol Chem. 1999 Mar 12;274(11):7172-81
pubmed: 10066777
Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1355-63
pubmed: 15272157
J Virol. 2003 Nov;77(22):12022-32
pubmed: 14581539
J Struct Biol. 2001 Dec;136(3):190-200
pubmed: 12051899
J Virol. 2007 Apr;81(7):3563-73
pubmed: 17215278
J Virol. 2002 Nov;76(22):11645-58
pubmed: 12388725
Mol Cell. 2000 Feb;5(2):255-66
pubmed: 10882067
Nucleic Acids Res. 2003 Jul 1;31(13):3320-3
pubmed: 12824317
N Engl J Med. 2013 May 2;368(18):1670-3
pubmed: 23635048
J Cell Biol. 1983 Sep;97(3):644-51
pubmed: 6688423
Mol Ther Methods Clin Dev. 2017 Mar 08;5:1-12
pubmed: 28480299
Nat Methods. 2012 Sep;9(9):853-4
pubmed: 22842542
Elife. 2013 Apr 02;2:e00435
pubmed: 23577234
Microbiol Rev. 1994 Sep;58(3):491-562
pubmed: 7968923
Structure. 2006 Jan;14(1):63-73
pubmed: 16407066
J Virol. 2013 Aug;87(15):8582-90
pubmed: 23720725
Mol Syst Biol. 2011 Oct 11;7:539
pubmed: 21988835
J Struct Biol. 2009 Apr;166(1):95-102
pubmed: 19263523
J Virol. 2010 Oct;84(19):9775-82
pubmed: 20631130
J Struct Biol. 2015 Nov;192(2):216-21
pubmed: 26278980
Am J Trop Med Hyg. 2018 May;98(5):1472-1477
pubmed: 29557336
J Virol. 2019 Mar 5;93(6):
pubmed: 30602608
J Biol Chem. 2008 Nov 7;283(45):31237-45
pubmed: 18757372
J Virol. 1998 Sep;72(9):7349-56
pubmed: 9696831
Methods Mol Biol. 2014;1117:401-43
pubmed: 24357374
Nature. 1986 Apr 10-16;320(6062):533-5
pubmed: 3960136
Nature. 2010 Dec 2;468(7324):709-12
pubmed: 21124458
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16026-31
pubmed: 21896745
J Virol. 2011 Sep;85(18):9327-33
pubmed: 21752915
J Virol. 1987 May;61(5):1301-9
pubmed: 3553612
Cold Spring Harb Symp Quant Biol. 1962;27:1-24
pubmed: 14019094
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
Virology. 2006 Mar 30;347(1):183-90
pubmed: 16380143
Biochemistry. 1975 Jan 14;14(1):85-8
pubmed: 122810
Virology. 2005 Feb 20;332(2):511-8
pubmed: 15680416
Virology. 2000 Oct 10;276(1):93-103
pubmed: 11021998
Cell Host Microbe. 2011 Aug 18;10(2):97-104
pubmed: 21843867
Cell Rep. 2018 Dec 11;25(11):3136-3147.e5
pubmed: 30540945
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Virology. 1990 Mar;175(1):274-81
pubmed: 2408229
Structure. 1996 May 15;4(5):531-41
pubmed: 8736552
PLoS Negl Trop Dis. 2014 Feb 20;8(2):e2719
pubmed: 24587470
Cell. 1995 Feb 24;80(4):621-30
pubmed: 7867069
J Virol. 1998 Sep;72(9):7357-66
pubmed: 9696832
J Virol. 1994 Dec;68(12):8064-70
pubmed: 7966596
J Struct Biol. 2005 Jul;151(1):41-60
pubmed: 15890530
Am J Trop Med Hyg. 1995 Jan;52(1):8-13
pubmed: 7856830
J Virol. 2012 Jun;86(11):6084-96
pubmed: 22457519
Nat Microbiol. 2019 Jan;4(1):187-197
pubmed: 30455470
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Acta Crystallogr D Biol Crystallogr. 2000 Oct;56(Pt 10):1341-9
pubmed: 10998631
EMBO J. 2011 Aug 09;30(18):3854-63
pubmed: 21829169
Clin Diagn Lab Immunol. 2000 Nov;7(6):915-9
pubmed: 11063498
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
J Struct Biol. 2012 Dec;180(3):519-30
pubmed: 23000701