PXD061924

PXD061924 is an original dataset announced via ProteomeXchange.

Title	New structural insights into the control of the retinoic acid receptors RAR/RXR by DNA, ligands and transcriptional coregulators
Description	Retinoic acid receptors (RARs) are ligand-dependent transcription factors essential for various biological processes, including embryogenesis, differentiation, and apoptosis. RARs function as heterodimers with retinoid X receptors (RXRs) and regulate gene expression via retinoic acid response elements (RAREs). Their transcriptional activity is modulated by coregulators, with corepressors maintaining repression in the absence of ligand and coactivators enabling transcription upon ligand binding. Structural studies reveal that DNA binding induces conformational changes affecting coregulator interactions. However, the precise structural organization of RAR/RXR-coregulator complexes and the allosteric influence of DNA on receptor function remain incompletely understood. Our study presents an integrative analysis of the RAR/RXR heterodimer bound to four distinct RAREs (DR0, DR1, DR5, and IR0) in complex with either a corepressor (NCoR) or a coactivator (TIF-2) nuclear receptor interaction domain. By combining SAXS data and molecular dynamics simulations, the findings reveal that the heterodimer adopts distinct conformations depending on the DNA sequence, influencing interdomain distances and receptor interactions. Additionally, HDX-MS analysis uncovers the dynamic interplay between ligand, DNA, and coregulator binding. Notably, the study provides new insights into the structural features of coregulator proteins and highlights the allosteric influence of RAREs on receptor function.
HostingRepository	PRIDE
AnnounceDate	2025-10-03
AnnouncementXML	Submission_2025-10-03_10:01:58.831.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dmitry Loginov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro; solariX

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-17 07:52:44	ID requested
⏵ 1	2025-10-03 10:01:59	announced

10.1093/NAR/GKAF967;

submitter keyword: receptor interaction, retinoid X receptor, DNA binding,retinoic acid receptor

Petr Man
contact affiliation	Institute of Microbiology of the CAS
contact email	pman@biomed.cas.cz
lab head
Dmitry Loginov
contact affiliation	BioCeV - Institute of Microbiology of the CAS
contact email	dloginov@jcu.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061924
     1. Label: PRIDE project
     2. Name: New structural insights into the control of the retinoic acid receptors RAR/RXR by DNA, ligands and transcriptional coregulators