PXD062177
PXD062177 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Structural Heterogeneity of Proteoform-Ligand Complexes in AMP-Activated Protein Kinase Uncovered by Integrated Top-Down Mass Spectrometry |
| Description | AMP-activated protein kinase (AMPK) is a heterotrimeric complex that serves as a master regulator of cellular metabolism, making it a prominent drug target for various diseases. Post-translational modifications (PTMs) and ligand binding significantly affect the activity and function of AMPK. However, the dynamic interplay of PTMs, non-covalent interactions, and higher-order structures of the kinase complex remain poorly understood. Herein, we report the structural heterogeneity of the AMPK complex arising from ligand binding and proteoforms, protein products derived from PTMs, alternative splicing, and genetic variants, using integrated native and denatured top-down mass spectrometry (TDMS). The fully intact AMPK heterotrimeric complex exhibits heterogeneity due to phosphorylation and multiple adenosine monophosphate (AMP) binding states. Native TDMS provides valuable insights into the higher-order structure of AMPK, subunit composition, and AMP binding stoichiometry, whilst denatured TDMS characterizes the proteoforms and localizes the phosphorylation site. This is the first study to structurally characterize AMPK proteoform-ligand complexes. Notably, using native TDMS and AlphaFold, we resolve a flexible regulatory region that has been difficult to visualize with traditional structural biology tools. These findings offer new perspectives on protein kinase regulation and establish a powerful framework for elucidating other kinase complexes. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-09-10 |
| AnnouncementXML | Submission_2025-09-10_11:57:28.042.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Hsin-Ju Chan |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Phospho |
| Instrument | solariX; impact II |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-03-24 11:53:57 | ID requested | |
| ⏵ 1 | 2025-09-10 11:57:28 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: top-down mass spectrometry, native top-down mass spectrometry, AMP-activated protein kinase, post-translational modifications, protein-ligand binding, DatasetType:Proteomics |
Contact List
| Ying Ge | |
|---|---|
| contact affiliation | University of Wisconsin-Madison |
| contact email | ge2@wisc.edu |
| lab head | |
| Hsin-Ju Chan | |
| contact affiliation | University of Wisconsin-Madison |
| contact email | hchan48@wisc.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/v09/MSV000097430/ |
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