Structural and functional basis of VLDLR receptor usage by Eastern equine encephalitis virus.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
15 Nov 2023
15 Nov 2023
Historique:
pubmed:
28
11
2023
medline:
28
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
The very low-density lipoprotein receptor (VLDLR) is comprised of eight LDLR type A (LA) domains and supports entry of distantly related Eastern equine encephalitis (EEEV) and Semliki Forest (SFV) alphaviruses. Here, by resolving multiple cryo-electron microscopy structures of EEEV-VLDLR complexes and performing mutagenesis and functional studies, we show that EEEV uses multiple sites (E1/E2 cleft and E2 A domain) to engage different LA domains simultaneously. However, no single LA domain is necessary or sufficient to support efficient EEEV infection, highlighting complexity in domain usage. Whereas all EEEV strains show conservation of two VLDLR binding sites, the EEEV PE-6 strain and other EEE complex members feature a single amino acid substitution that mediates binding of LA domains to an additional site on the E2 B domain. These structural and functional analyses informed the design of a minimal VLDLR decoy receptor that neutralizes EEEV infection and protects mice from lethal challenge.
Identifiants
pubmed: 38014196
doi: 10.1101/2023.11.15.567188
pmc: PMC10680733
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201700060C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095436
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141436
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142790
Pays : United States
Références
Nature. 2018 May;557(7706):570-574
pubmed: 29769725
J Virol. 2017 Jun 26;91(14):
pubmed: 28468884
Nat Methods. 2022 Jun;19(6):679-682
pubmed: 35637307
Cell Rep. 2019 Sep 3;28(10):2647-2658.e5
pubmed: 31484075
Cell. 2019 Jun 13;177(7):1714-1724.e12
pubmed: 31080063
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Lancet Infect Dis. 2022 Aug;22(8):1210-1220
pubmed: 35568049
PLoS Negl Trop Dis. 2022 May 9;16(5):e0010081
pubmed: 35533188
Nature. 2022 Feb;602(7897):475-480
pubmed: 34929721
Nat Rev Rheumatol. 2012 May 08;8(7):420-9
pubmed: 22565316
Emerg Infect Dis. 2013 Feb;19(2):194-201; quiz 352
pubmed: 23343480
J Virol. 2017 Jun 9;91(13):
pubmed: 28404855
Microbiol Rev. 1994 Sep;58(3):491-562
pubmed: 7968923
J Virol. 2013 Aug;87(15):8582-90
pubmed: 23720725
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27637-27645
pubmed: 33087569
Nat Commun. 2018 Mar 12;9(1):1029
pubmed: 29531262
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Am J Trop Med Hyg. 2018 May;98(5):1472-1477
pubmed: 29557336
Nature. 2021 Oct;598(7882):672-676
pubmed: 34646020
Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):8890-8899
pubmed: 32245806
Cell. 2015 Nov 19;163(5):1095-1107
pubmed: 26553503
Cell Host Microbe. 2020 Mar 11;27(3):428-440.e9
pubmed: 32075743
PLoS One. 2011;6(6):e20161
pubmed: 21731610
Cell Mol Life Sci. 2006 Oct;63(19-20):2196-212
pubmed: 16964582
Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13898-903
pubmed: 26504196
Proc Natl Acad Sci U S A. 2011 Nov 22;108(47):18949-53
pubmed: 22065763
Cell. 2021 Aug 19;184(17):4414-4429.e19
pubmed: 34416146
Cell Rep. 2015 Dec 22;13(11):2553-2564
pubmed: 26686638
PLoS Pathog. 2020 May 4;16(5):e1008517
pubmed: 32365139
J Virol. 2014 Feb;88(4):2035-46
pubmed: 24307590
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. 2001 Jul;75(14):6303-9
pubmed: 11413296
Nature. 2021 Aug;596(7873):583-589
pubmed: 34265844
J Virol. 2017 Aug 24;91(18):
pubmed: 28679762
J Immunol. 1947 Jan;55(1):41-52
pubmed: 20285155
Vet Microbiol. 2010 Jan 27;140(3-4):281-6
pubmed: 19775836
Cell Host Microbe. 2020 Nov 11;28(5):699-711.e7
pubmed: 32783883
Nature. 2020 Dec;588(7837):308-314
pubmed: 33208938
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
Nature. 2021 Oct;598(7882):677-681
pubmed: 34646021
Springerplus. 2016 Jan 12;5:27
pubmed: 26788439
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):
pubmed: 34507983
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Virology. 2005 Feb 20;332(2):511-8
pubmed: 15680416
Vaccines (Basel). 2020 Jun 03;8(2):
pubmed: 32503232
Virology. 2000 Oct 10;276(1):93-103
pubmed: 11021998
Cell Rep. 2018 Dec 11;25(11):3136-3147.e5
pubmed: 30540945
Elife. 2018 Nov 09;7:
pubmed: 30412051
Nature. 2010 Dec 2;468(7324):705-8
pubmed: 21124457
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530
pubmed: 29872003
Cell. 1995 Feb 24;80(4):621-30
pubmed: 7867069
Virol J. 2019 Jan 5;16(1):2
pubmed: 30611287
Nat Struct Mol Biol. 2004 May;11(5):429-34
pubmed: 15064754
Virology. 1990 Mar;175(1):110-23
pubmed: 2155505
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9095-9
pubmed: 8415660
J Virol. 1998 Sep;72(9):7357-66
pubmed: 9696832
J Infect Dis. 2004 Mar 15;189(6):1013-7
pubmed: 14999604
Sci Transl Med. 2019 May 15;11(492):
pubmed: 31092692
Nat Microbiol. 2019 Jan;4(1):187-197
pubmed: 30455470
J Virol. 2014 Mar;88(5):2385-97
pubmed: 24371059
Proteins. 2021 Apr;89(4):436-449
pubmed: 33249652
Cell. 2001 Apr 6;105(1):137-48
pubmed: 11301009
Cell. 2020 Dec 23;183(7):1884-1900.e23
pubmed: 33301709
J Clin Invest. 2023 Jan 17;133(2):
pubmed: 36647825
Cell. 2019 Jun 13;177(7):1725-1737.e16
pubmed: 31080061
Virol J. 2017 Feb 7;14(1):25
pubmed: 28173871
Cell Host Microbe. 2015 Jul 8;18(1):86-95
pubmed: 26159721
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774
Biochemistry. 2010 Feb 16;49(6):1207-16
pubmed: 20030366
Cell. 2023 May 11;186(10):2208-2218.e15
pubmed: 37098345
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
PLoS Pathog. 2013;9(4):e1003312
pubmed: 23637602
Nucleic Acids Res. 2008 Apr;36(7):2295-300
pubmed: 18287115