_____ _ _ _
| __ \ (_) (_) | |
| |__) |__ __ _ __ __ _ ___ | |_
| _ / \ \ / /| |\ \ / /| |/ __|| __|
| | \ \ \ v / | | \ V / | |\__ \| |_
|_| \_\ > < |_| \_/ |_||___/ \__|
/ ^ \
/_/ \_\
TRENDING OPEN SCIENCE
-------------
The SARS-CoV-2 spike protein binds and modulates estrogen receptors
--------
By
Oscar Solis
Andrea R. Beccari
Daniela Iaconis
Carmine Talarico
Camilo A. Ruiz-Bedoya
Jerome C. Nwachukwu
Annamaria Cimini
Vanessa Castelli
Riccardo Bertini
Monica Montopoli
Veronica Cocetta
Stefano Borocci
Ingrid G. Prandi
Kelly Flavahan
Melissa Bahr
Anna Napiorkowski
Giovanni Chillemi
Masato Ooka
Xiaoping Yang
Shiliang Zhang
Menghang Xia
Wei Zheng
Jordi Bonaventura
Martin G. Pomper
Jody E. Hooper
Marisela Morales
Avi Z Rosenberg
Kendall W Nettles
Sanjay K Jain
Marcello Allegretti
Michael Michaelides
DOI: 10.1101/2022.05.21.492920
On bioRxiv: https://biorxiv.org/content/10.1101/2022.05.21.492920v1
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike
(S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell
nfection. Molecular interactions between the transduced S and
endogenous proteins likely occur post-infection, but such interactions
are not well understood. We used an unbiased primary screen to profile
the binding of full-length S against >9,000 human proteins and found
n a secondary assay, we used bioinformatics, supercomputing, and
experimental assays to identify a highly conserved and functional
nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit
and an S-ER binding mode. In cultured cells, S DNA transfection
ncreased ER cytoplasmic accumulation, and S treatment induced ER-
multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using
[18F]fluoroestradiol (FES) localized lung pathology with increased ER
lung levels. Postmortem experiments in lung tissues from SARS-
CoV-2-infected hamsters and humans confirmed an increase in
cytoplasmic ER expression and its colocalization with S protein in
alveolar macrophages. These findings describe the discovery and
characterization of a novel S-ER interaction, imply a role for S as an
NRC, and are poised to advance knowledge of SARS-CoV-2 biology,
COVID-19 pathology, and mechanisms of sex differences in the pathology
of infectious disease.
---
RANKS:
- Overall rank: 35479
- Rank in immunology: 1329
______________________________________________________________________
Served by Flask-Gopher/2.0.0
