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PXD036076

PXD036076 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLigand-induced shifts in conformational ensembles that predict transcriptional activation
DescriptionNuclear receptors function as ligand-regulated transcription factors whose ability to regulate diverse physiological processes is closely linked with conformational changes induced upon ligand binding. Understanding how conformational populations of nuclear receptors are shifted by various ligands could illuminate strategies for the design of synthetic modulators to regulate specific transcriptional programs. Here, we investigate ligand-induced conformational changes using a reconstructed, ancestral nuclear receptor. By making substitutions at a key position, we engineer receptor variants with altered ligand specificities. We use atomistic molecular dynamics (MD) simulations with enhanced sampling to generate ensembles of wildtype and engineered receptors in combination with multiple ligands, followed by conformational analysis and prediction of ligand activity. We combine cellular and biophysical experiments to allow correlation of MD-based predictions with functional ligand profiles, as well as elucidation of mechanisms underlying altered transcription in receptor variants. We determine that conformational ensembles accurately predict ligand responses based on observed population shifts, even within engineered receptors that were constitutively active or transcriptionally unresponsive in experiments. These studies provide a platform which will allow structural characterization of physiologically-relevant conformational ensembles, as well as provide the ability to design and predict transcriptional responses in novel ligands.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:40:07.649.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSABAB HASAN KHAN
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-16 05:51:10ID requested
12022-10-12 09:26:38announced
22024-10-22 05:40:08announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: LC-MSMS
Contact List
C. Denise Okafor
contact affiliationDepartment of Biochemistry and Molecular Biology, Pennsylvania State University
contact emailcdo5093@psu.edu
lab head
SABAB HASAN KHAN
contact affiliationPennsylvania State University
contact emailshk5169@psu.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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