PXD028039

PXD028039 is an original dataset announced via ProteomeXchange.

Title	The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities
Description	The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, the functional oligomeric state of the full-length receptor, which is essential for its transcriptional activity, remains disputed. Here we present five new crystal structures of agonist-bound GR-LBD, along with a thorough analysis of previous structural work. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution and quantitative fluorescence microscopy in live cells. Our results highlight the relevance of non-canonical dimerization modes for GR, especially of contacts made by loop L1-3 residues such as Tyr545. Our work unveils likely pathophysiologically relevant quaternary assemblies of the nuclear receptor with important implications for glucocorticoid action and drug design.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:39:15.948.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marina Gay
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-19 21:50:41	ID requested
1	2023-03-11 00:19:02	announced
⏵ 2	2023-11-14 08:39:16	announced	2023-11-14: Updated project metadata.

Jim, é, nez-Panizo A, Alegre-Mart, í A, Tettey TT, Fettweis G, Abella M, Ant, ó, n R, Johnson TA, Kim S, Schiltz RL, N, ú, ñ, ez-Barrios I, Font-D, í, az J, Caelles C, Valledor AF, P, é, rez P, Rojas AM, Fern, á, ndez-Recio J, Presman DM, Hager GL, Fuentes-Prior P, Est, é, banez-Perpi, ñ, á E, The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities. Nucleic Acids Res, 50(22):13063-13082(2022) [pubmed]

submitter keyword: glucocorticoid receptor, mass spectrometry, ligand-binding domain, sectors, X-ray crystallography, fluorescence microscopy, mutations, quaternary structure, glucocorticoids, homodimerization

Eva Estébanez-Perpiñá
contact affiliation	Structural Biology of Nuclear Receptors, Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona (UB), 08028 Barcelona, Spain
contact email	evaestebanez@ub.edu
lab head
Marina Gay
contact affiliation	Institute for Research in Biomedicine
contact email	marina.gay@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/2023/03/PXD028039

PRIDE project URI

• PRIDE
  1. PXD028039
     1. Label: PRIDE project
     2. Name: The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities