Evidence map›Paper›PMID 40082595›Full record

ArticleCommunications biology2025

Structural basis for the asymmetric binding of coactivator SRC1 to FXR-RXRα and allosteric communication within the complex.

Yanan Sheng, Yaoting Guo, Beibei Zhao, Mingze Sun, Yan Dong, Yue Yin, Yanwu Wang, Chao Peng, Yong Xu, Na Wang and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yanan Sheng *Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
Yaoting Guo *State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Beibei ZhaoDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
Mingze SunState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Yan DongState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Yue YinNational Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Science, Shanghai, 201210, China.ORCID http://orcid.org/0000-0002-7693-3910
Yanwu WangBaizhen Biotechnologies Inc., 430074, Wuhan, China.
Chao PengBaizhen Biotechnologies Inc., 430074, Wuhan, China.
Yong XuState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Na WangState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. wang_na@gibh.ac.cn.ORCID http://orcid.org/0009-0000-4095-3963
Jinsong LiuDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China. liu_jinsong@gibh.ac.cn.ORCID http://orcid.org/0000-0003-2317-0558

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Farnesoid X receptor (FXR) is a promising target for treatment of metabolic associated fatty liver disease (MAFLD). 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.

Indexed as

Nuclear Receptor Coactivator 1Receptors, Cytoplasmic and NuclearRetinoid X Receptor alphaAllosteric RegulationDNAHumansModels, MolecularProtein BindingReceptor, Farnesoid X-ActivatedDNANCOA1 protein, humanNuclear Receptor Coactivator 1Receptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearRetinoid X Receptor alpha

Identifiers

PMID40082595
PMCPMC11906777

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.