The marionette mechanism of domain–domain communication in the antagonist, agonist, and coactivator responses of the estrogen receptor

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dc.citation.articleNumbere2216906120en_US
dc.citation.issueNumber6en_US
dc.citation.journalTitleProceedings of the National Academy of Sciencesen_US
dc.citation.volumeNumber120en_US
dc.contributor.authorChen, Xunen_US
dc.contributor.authorJin, Shikaien_US
dc.contributor.authorChen, Mingchenen_US
dc.contributor.authorBueno, Carlosen_US
dc.contributor.authorWolynes, Peter G.en_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.contributor.orgSystems, Synthetic, and Physical Biologyen_US
dc.date.accessioned2023-02-23T18:46:12Zen_US
dc.date.available2023-02-23T18:46:12Zen_US
dc.date.issued2023en_US
dc.description.abstractThe human estrogen receptor α (hERα) is involved in the regulation of growth, development, and tissue homeostasis. Agonists that bind to the receptor’s ligand-binding domain (LBD) lead to recruitment of coactivators and the enhancement of gene expression. In contrast, antagonists bind to the LBD and block the binding of coactivators thus decreasing gene expressions. In this work, we carry out simulations using the AWSEM (Associative memory, Water mediated, Structure and Energy Model)-Suite force field along with the 3SPN.2C force field for DNA to predict the structure of hERα and study its dynamics when binding to DNA and coactivators. Using simulations of antagonist-bound hERα and agonist-bound hERα by themselves and also along with bound DNA and coactivators, principal component analyses and free energy landscape analyses capture the pathway of domain–domain communication for agonist-bound hERα. This communication is mediated through the hinge domains that are ordinarily intrinsically disordered. These disordered segments manipulate the hinge domains much like the strings of a marionette as they twist in different ways when antagonists or agonists are bound to the ligand-binding domain.en_US
dc.identifier.citationChen, Xun, Jin, Shikai, Chen, Mingchen, et al.. "The marionette mechanism of domain–domain communication in the antagonist, agonist, and coactivator responses of the estrogen receptor." <i>Proceedings of the National Academy of Sciences,</i> 120, no. 6 (2023) PNAS: https://doi.org/10.1073/pnas.2216906120.en_US
dc.identifier.digitalpnas-2216906120en_US
dc.identifier.doihttps://doi.org/10.1073/pnas.2216906120en_US
dc.identifier.urihttps://hdl.handle.net/1911/114477en_US
dc.language.isoengen_US
dc.publisherPNASen_US
dc.rightsThis article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleThe marionette mechanism of domain–domain communication in the antagonist, agonist, and coactivator responses of the estrogen receptoren_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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