PXD056400

PXD056400 is an original dataset announced via ProteomeXchange.

Title	Structural proteomics defines a sequential priming mechanism for the progesterone receptor (HDX-MS)
Description	The progesterone receptor (PR) is a steroid-responsive nuclear receptor with two isoforms: PR-A and PR-B. Disruption of PR-A:PR-B signaling is associated with breast cancer through interactions with oncogenic co-regulatory proteins (CoRs). However, molecular details of isoform-specific PR-CoR interactions remain poorly understood. Using structural mass spectrometry, we investigate the sequential binding mechanism of purified full-length PR and intact CoRs, steroid receptor coactivator 3 (SRC3) and p300, as complexes on target DNA. Our findings reveal selective CoR NR-box binding by PR and novel interaction surfaces between PR and CoRs during complex assembly, providing a structural basis for CoR sequential binding on PR. Antagonist-bound PR showed persistent CoR interactions, challenging the classical model of nuclear receptor activation and repression. Collectively, we offer a peptide-level perspective on the organization of the PR transcriptional complex and infer the mechanisms behind the interactions of these proteins, both in active and inactive conformations.
HostingRepository	PRIDE
AnnounceDate	2025-04-07
AnnouncementXML	Submission_2025-04-07_12:50:36.655.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthew Mann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-30 09:47:07	ID requested
⏵ 1	2025-04-07 12:50:37	announced

Dataset with its publication pending

submitter keyword: hydrogen-deuterium exchange, progesterone receptor, structural proteomics,HDX

Patrick R. Griffin
contact affiliation	Professor, Molecular Medicine & Scientific Director, The Wertheim UF Scripps Institute
contact email	pgriffin2@ufl.edu
lab head
Matthew Mann
contact affiliation	Skaggs Graduate School, Scripps Research Department of Molecular Medicine, The Wertheim UF Scripps Institute
contact email	mmann@scripps.edu
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/2025/04/PXD056400

PRIDE project URI

• PRIDE
  1. PXD056400
     1. Label: PRIDE project
     2. Name: Structural proteomics defines a sequential priming mechanism for the progesterone receptor (HDX-MS)