PXD065782

PXD065782 is an original dataset announced via ProteomeXchange.

Title	The multimerization pathway of the glucocorticoid receptor
Description	The glucocorticoid receptor (GR/NR3C1), a ligand-activated transcription factor belonging to the nuclear receptor (NR) superfamily, is vital for life. Like other NRs, GR features an intrinsically disordered N-terminal domain (NTD) followed by a highly conserved DNA-binding domain (DBD) and a hormone- or ligand-binding domain (LBD), separated by a long linker. While the receptor's quaternary structure is critical for its transcriptional activity, its precise multimeric organization has remained elusive. Here, we conducted a comprehensive crosslinking-mass spectrometry (XL-MS) analysis using cleavable crosslinkers (DSSO and DSBU) to investigate the quaternary structure of the GR DBD-linker-LBD tandem. Our results strongly support a model of non-canonical receptor multimerization, revealing that GR monomers arrange in a parallel fashion through interactions involving residues within the LBD's L1-3 loop (evidenced by XLs K576-K576’ and K579-K579’). These parallel, non-canonical dimers then further associate to form dimers-of-dimers, mediated by contacts within the H9/L9-10/H10 region (e.g., K695-K695’). This study provides unambiguous evidence for a novel GR multimerization mechanism and has important implications for the design of glucocorticoids with fewer side effects.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-26_17:17:11.653.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marta Vilaseca
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	crosslinked L-lysine residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-04 03:51:28	ID requested
⏵ 1	2025-10-26 17:17:12	announced

10.1093/nar/gkaf1003;

Alegre-Mart, í A, Jim, é, nez-Panizo A, Lafuente AL, Johnson TA, Montoya-Novoa I, Peralta-Moreno MN, Montany, à, -Valluguera P, Ponset, í, -Pons J, Abella M, Kim S, D, í, az M, Vilaseca M, P, é, rez P, Fern, á, ndez-Recio J, Rubio-Mart, í, nez J, Presman DM, Hager GL, Fuentes-Prior P, Est, é, banez-Perpi, ñ, á E, The multimerization pathway of the glucocorticoid receptor. Nucleic Acids Res, 53(19):(2025) [pubmed]

submitter keyword: glucocorticoid receptor,transcription factor, glucocorticoid resistance, steroid receptor, nuclear receptor, quaternary structure, homodimerization

Marta Vilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain.
contact email	masspe@irbbarcelona.org
lab head
Marta Vilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain
contact email	masspe@irbbarcelona.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD065782

PRIDE project URI

• PRIDE
  1. PXD065782
     1. Label: PRIDE project
     2. Name: The multimerization pathway of the glucocorticoid receptor