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sciadv.add4150.pdf (8.51 MB)

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2022-12-02

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cc by-nc (c) Solis, Oscar et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/192288

The SARS-CoV-2 spike protein binds and modulates estrogen receptors

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https://doi.org/10.1126/sciadv.add4150

Resum

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.

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SARS-CoV-2, Pandèmia de COVID-19, 2020-, Fixació de proteïnes

Matèries (anglès)

SARS-CoV-2, COVID-19 Pandemic, 2020-, Protein binding

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Neurociències (UBNeuro))

Citació

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. The SARS-CoV-2 spike protein binds and modulates estrogen receptors. _Science Advances_. 2022. Vol. 8, núm. 48, pàgs. eadd4150. [consulta: 26 de febrer de 2026]. ISSN: 2375-2548. [Disponible a: https://hdl.handle.net/2445/192288]

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