PXD057549
PXD057549 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | A tethering mechanism underlies Pin1-catalyzed proline cis-trans isomerization at a noncanonical site |
Description | The prolyl isomerase Pin1 catalyzes the cis-trans isomerization of proline peptide bonds, a non-covalent post-translational modification that influences cellular and molecular processes, including protein-protein interactions. Pin1 is a two-domain enzyme containing a WW domain that recognizes phosphorylated serine/threonine-proline (pS/pT-P) canonical motifs and an enzymatic PPIase domain that catalyzes proline cis-trans isomerization of pS/pT-P motifs. Here, we show that Pin1 uses a tethering mechanism to bind and catalyze proline cis-trans isomerization of a noncanonical motif in the disordered N-terminal activation function-1 (AF-1) domain of the human nuclear receptor PPARgamma. NMR reveals multiple Pin1 binding regions within the PPARgamma AF-1, including a canonical motif that when phosphorylated by the kinase ERK2 (pS112-P113) binds the Pin1 WW domain with high affinity. NMR methods reveal that Pin1 also binds and accelerates cis-trans isomerization of a noncanonical motif containing a tryptophan-proline motif (W39-P40) previously shown to be involved in an interdomain interaction with the C-terminal ligand-binding domain (LBD). Cellular transcription studies combined with mutagenesis and Pin1 inhibitor treatment reveal a functional role for Pin1-mediated acceleration ofcis-trans isomerization of the W39-P40 motif. Our data inform a refined model of the Pin1 catalytic mechanism where the WW domain binds a canonical pS/T-P motif and tethers Pin1 to the target, which enables the PPIase domain to exert catalytic cis-trans isomerization at a distal noncanonical site. |
HostingRepository | MassIVE |
AnnounceDate | 2025-04-28 |
AnnouncementXML | Submission_2025-04-28_08:26:00.416.xml |
DigitalObjectIdentifier | |
ReviewLevel | Non peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | George Tsaprailis |
SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
ModificationList | Phospho; Deamidated; Carbamidomethyl; Oxidation |
Instrument | Orbitrap Fusion ETD |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2024-11-05 12:23:43 | ID requested | |
⏵ 1 | 2025-04-28 08:26:00 | announced |
Publication List
no publication |
Keyword List
submitter keyword: The prolyl isomerase Pin1, DatasetType:Proteomics |
Contact List
Douglas Kojetin | |
---|---|
contact affiliation | Vanderbilt University |
contact email | douglas.kojetin@Vanderbilt.Edu |
lab head | |
George Tsaprailis | |
contact affiliation | The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology |
contact email | gtsaprailis@ufl.edu |
dataset submitter |
Full Dataset Link List
MassIVE dataset URI |
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://massive-ftp.ucsd.edu/v07/MSV000096300/ |