The SARS-CoV-2 spike protein binds and modulates estrogen receptors.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
02 12 2022
02 12 2022
Historique:
entrez:
30
11
2022
pubmed:
1
12
2022
medline:
3
12
2022
Statut:
ppublish
Résumé
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 as its primary infection mechanism. Interactions between S and endogenous proteins occur after infection but are not well understood. We profiled binding of S against >9000 human proteins and found an interaction between S and human estrogen receptor α (ERα). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ERα lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ERα and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ERα interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology.
Identifiants
pubmed: 36449624
doi: 10.1126/sciadv.add4150
pmc: PMC9710872
doi:
Substances chimiques
spike protein, SARS-CoV-2
0
Spike Glycoprotein, Coronavirus
0
Receptors, Estrogen
0
Estrogen Receptor alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eadd4150Subventions
Organisme : NIAID NIH HHS
ID : R01 AI153349
Pays : United States
Commentaires et corrections
Type : UpdateOf
Références
Int J Mol Sci. 2021 May 22;22(11):
pubmed: 34067272
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5930-5
pubmed: 10823945
Anticancer Res. 2007 May-Jun;27(3B):1393-9
pubmed: 17595753
Nucleic Acids Res. 2021 Jan 8;49(D1):D605-D612
pubmed: 33237311
Ann Oncol. 2021 May;32(5):676-677
pubmed: 33524477
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Methods Mol Biol. 2012;816:187-202
pubmed: 22130930
Int J Mol Sci. 2021 Oct 26;22(21):
pubmed: 34768939
Curr Opin Pharmacol. 2013 Aug;13(4):576-81
pubmed: 23731522
J Comput Chem. 2004 Jul 15;25(9):1157-74
pubmed: 15116359
Front Immunol. 2020 Jun 05;11:1312
pubmed: 32582222
Arch Biochem Biophys. 2007 Apr 15;460(2):206-12
pubmed: 17254542
Cell Death Differ. 2022 Jan;29(1):156-166
pubmed: 34404919
Front Immunol. 2018 Aug 27;9:1931
pubmed: 30210492
Endocr Relat Cancer. 2006 Sep;13(3):863-73
pubmed: 16954435
Platelets. 2021 Jul 4;32(5):690-696
pubmed: 33561381
Nat Protoc. 2020 May;15(5):1829-1852
pubmed: 32269383
mBio. 2021 Aug 31;12(4):e0097421
pubmed: 34253053
Science. 2020 Nov 13;370(6518):861-865
pubmed: 33082294
Breast Cancer. 1998 Apr 25;5(2):99-106
pubmed: 11091634
Physiol Rev. 2007 Jul;87(3):905-31
pubmed: 17615392
Acta Pharmacol Sin. 2020 Sep;41(9):1141-1149
pubmed: 32747721
J Immunol. 2017 May 15;198(10):4046-4053
pubmed: 28373583
Cell. 2020 Apr 16;181(2):281-292.e6
pubmed: 32155444
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713
pubmed: 26574453
Chembiochem. 2010 Nov 2;11(16):2251-4
pubmed: 20922740
Vascul Pharmacol. 2021 Apr;137:106823
pubmed: 33232769
Trends Biochem Sci. 2005 Feb;30(2):66-9
pubmed: 15691650
Virus Res. 2009 Jun;142(1-2):19-27
pubmed: 19185596
J Microbiol. 2021 Feb;59(2):124-131
pubmed: 33527314
J Immunol. 2017 Sep 1;199(5):1573-1583
pubmed: 28760880
Pharmacol Ther. 2018 Jun;186:1-24
pubmed: 29289555
Endocrinology. 2010 Jan;151(1):174-84
pubmed: 19952273
Nat Microbiol. 2020 Apr;5(4):562-569
pubmed: 32094589
Proc Natl Acad Sci U S A. 2020 May 26;117(21):11727-11734
pubmed: 32376634
Cell Immunol. 2018 Aug;330:86-90
pubmed: 29370889
BMC Cell Biol. 2010 Dec 10;11:98
pubmed: 21143970
J Med Virol. 2020 Apr;92(4):418-423
pubmed: 31967327
Thromb Res. 2021 May;201:23-29
pubmed: 33631519
Adv Exp Med Biol. 2021;1303:243-273
pubmed: 33788197
Am J Pathol. 2007 Apr;170(4):1136-47
pubmed: 17392154
Genes Dev. 1998 Nov 1;12(21):3357-68
pubmed: 9808623
Nat Med. 2020 Apr;26(4):529-534
pubmed: 32066976
Crit Rev Oncol Hematol. 2004 Apr;50(1):3-22
pubmed: 15094156
Nat Commun. 2020 Mar 27;11(1):1620
pubmed: 32221306
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7829-34
pubmed: 10869427
Int J Mol Sci. 2020 Dec 23;22(1):
pubmed: 33374797
Clin Infect Dis. 2021 Dec 6;73(11):e4208-e4213
pubmed: 32173725
iScience. 2020 Jun 26;23(6):101160
pubmed: 32405622
Malar J. 2014 Jun 13;13:230
pubmed: 24927627
ACS Cent Sci. 2020 Oct 28;6(10):1722-1734
pubmed: 33140034
Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):14930-5
pubmed: 22927406
Mol Imaging Biol. 2022 Feb;24(1):135-143
pubmed: 34424479
Int J Mol Sci. 2020 Apr 22;21(8):
pubmed: 32331343
Cell. 2020 Apr 16;181(2):271-280.e8
pubmed: 32142651
Front Nutr. 2021 Mar 18;8:649128
pubmed: 33816542
Cardiovasc Res. 2021 May 25;117(6):1557-1566
pubmed: 33705542
J Chem Phys. 2007 Jan 7;126(1):014101
pubmed: 17212484
Heliyon. 2021 Feb 02;7(2):e06187
pubmed: 33644468
Hum Pathol. 2005 Mar;36(3):303-9
pubmed: 15791576
EMBO J. 2000 Sep 1;19(17):4688-700
pubmed: 10970861
J Comput Chem. 2008 Mar;29(4):622-55
pubmed: 17849372
Biochim Biophys Acta. 2016 Sep;1863(9):2289-98
pubmed: 27288742
Cell. 2020 May 14;181(4):894-904.e9
pubmed: 32275855