PXD060593

PXD060593 is an original dataset announced via ProteomeXchange.

Title	Structural basis for the asymmetric binding of coactivator SRC1 to FXR-RXRα and allosteric communication within the complex
Description	In this study, we employed an integrative approach to investigate the interaction between FXR-RXRα-DNA complex and the entire coactivator SRC1-NRID (nuclear receptor interaction domain). We constructed a multi-domain model of FXR-RXRα-DNA, highlighting the interface between FXR-DBD and LBD. Using HDX-MS, XL-MS, and biochemical assays, we revealed the allosteric communications in FXR-RXRα-DNA upon agonist and DNA binding. We then demonstrated that SRC1 binds only to the coactivator binding surface of FXR within the FXR-RXRα heterodimer, with the NR-box2 and NR-box3 of SRC1 as the key binding motifs. Our findings, which provide the first model of SRC1-NRID in complex with FXR-RXRα-DNA, shed light on the molecular mechanism through which the coactivator asymmetrically interacts with nuclear receptors and provide structural basis for further understanding the function of FXR and its implications in diseases.
HostingRepository	iProX
AnnounceDate	2025-02-08
AnnouncementXML	Submission_2025-04-24_19:04:01.396.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Na Wang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-07 19:57:44	ID requested
1	2025-02-07 19:58:06	announced
⏵ 2	2025-04-24 19:04:02	announced	2025-04-25: Add Publication.

Sheng Y, Guo Y, Zhao B, Sun M, Dong Y, Yin Y, Wang Y, Peng C, Xu Y, Wang N, Liu J, and allosteric communication within the complex. Commun Biol, 8(1):425(2025) [pubmed]

submitter keyword: nuclear receptors, transcription factors, FXR, SRC1, integrative structural biology

Jinsong Liu
contact affiliation	Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
contact email	liu_jinsong@gibh.ac.cn
lab head
Na Wang
contact affiliation	Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
contact email	wang_na@gibh.ac.cn
dataset submitter

iProX dataset URI