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

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dc.citation.articleNumbere2216906120
dc.citation.issueNumber6
dc.citation.journalTitleProceedings of the National Academy of Sciences
dc.citation.volumeNumber120
dc.contributor.authorChen, Xun
dc.contributor.authorJin, Shikai
dc.contributor.authorChen, Mingchen
dc.contributor.authorBueno, Carlos
dc.contributor.authorWolynes, Peter G.
dc.contributor.orgCenter for Theoretical Biological Physics
dc.contributor.orgSystems, Synthetic, and Physical Biology
dc.date.accessioned2023-02-23T18:46:12Z
dc.date.available2023-02-23T18:46:12Z
dc.date.issued2023
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.
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.
dc.identifier.digitalpnas-2216906120
dc.identifier.doihttps://doi.org/10.1073/pnas.2216906120
dc.identifier.urihttps://hdl.handle.net/1911/114477
dc.language.isoeng
dc.publisherPNAS
dc.rightsThis article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleThe marionette mechanism of domain–domain communication in the antagonist, agonist, and coactivator responses of the estrogen receptor
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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