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Title: The SARS-CoV-2 spike protein binds and modulates estrogen receptors
Author: Solis, Oscar
Beccari, Andrea R.
Iaconis, Daniela
Talarico, Carmine
Ruiz Bedoya, Camilo A.
Nwachukwu, Jerome C.
Cimini, Annamaria
Castelli, Vanessa
Bertini, Riccardo
Montopoli, Monica
Cocetta, Veronica
Borocci, Stefano
Prandi, Ingrid G.
Flavahan, Kelly
Bahr, Melissa
Napiorkowski, Anna
Chillemi, Giovanni
Ooka, Masato
Yang, Xiaoping
Zhang, Shiliang
Xia, Menghang
Zheng, Wei
Bonaventura, Jordi
Pomper, Martin G.
Hooper, Jody E.
Morales, Marisela
Rosenberg, Avi Z.
Nettles, Kendall W.
Jain, Sanjay K.
Allegretti, Marcello
Michaelides, Michael
Keywords: SARS-CoV-2
Pandèmia de COVID-19, 2020-
Fixació de proteïnes
COVID-19 Pandemic, 2020-
Protein binding
Issue Date: 2-Dec-2022
Publisher: American Association for the Advancement of Science (AAAS)
Abstract: 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 alpha (ER alpha). Using bioinformatics, supercomputing, and experimental assays, we identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 sub-unit. In cultured cells, S DNA transfection increased ER alpha cytoplasmic accumulation, and S treatment induced ER-dependent biological effects. Non-invasive imaging in SARS-CoV-2-infected hamsters localized lung pathology with increased ER alpha lung levels. Postmortem lung experiments from infected hamsters and humans confirmed an increase in cytoplasmic ER alpha and its colocalization with S in alveolar macrophages. These findings describe the discovery of a S-ER alpha interaction, imply a role for S as an NRC, and advance knowledge of SARS-CoV-2 biology and coronavirus disease 2019 pathology.
Note: Reproducció del document publicat a:
It is part of: Science Advances, 2022, vol. 8, num. 48, p. eadd4150
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ISSN: 2375-2548
Appears in Collections:Articles publicats en revistes (Institut de Neurociències (UBNeuro))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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