PXD016401 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ |
Description | The repressive states of nuclear receptors (i.e., apo or bound to antagonists or inverse agonists) are poorly defined, despite the fact that nuclear receptors are a major drug target. Most ligand bound structures of nuclear receptors, including peroxisome proliferator-activated receptor γ (PPARγ), are similar to the apo structure. Here we use NMR, accelerated molecular dynamics and hydrogen-deuterium exchange mass spectrometry to define the PPARγ structural ensemble. We find that the helix 3 charge clamp positioning varies widely in apo and is stabilized by efficacious ligand binding. We also reveal a previously undescribed mechanism for inverse agonism involving an omega loop to helix switch which induces disruption of a tripartite salt-bridge network. We demonstrate that ligand binding can induce multiple structurally distinct repressive states. One state recruits peptides from two different corepressors, while another recruits just one, providing structural evidence of ligand bias in a nuclear receptor. |
HostingRepository | PRIDE |
AnnounceDate | 2020-01-13 |
AnnouncementXML | Submission_2020-01-13_05:53:13.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Bruce Pascal |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-11-22 01:58:18 | ID requested | |
⏵ 1 | 2020-01-13 05:53:15 | announced | |
Publication List
Heidari Z, Chrisman IM, Nemetchek MD, Novick SJ, Blayo AL, Patton T, Mendes DE, Diaz P, Kamenecka TM, Griffin PR, Hughes TS, . Nat Commun, 10(1):5825(2019) [pubmed] |
Keyword List
submitter keyword: nuclear receptor, PPARγ, protein structure |
Contact List
Patrick Griffin |
contact affiliation | Scripps Florida |
contact email | pgriffin@scripps.edu |
lab head | |
Bruce Pascal |
contact affiliation | Scripps Florida |
contact email | bpascal@scripps.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD016401
- Label: PRIDE project
- Name: Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ