PXD082934 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Activity-based profiling of primary brain cells identifies covalent allosteric modulators of HCN channels |
| Description | Chemical proteomics can provide global portraits of small molecule-protein interactions in native biological systems. However, such ligandability maps have, to date, mostly been restricted to readily accessible cancer cell lines or primary immune cells. Here, we describe an activity-based protein profiling (ABPP) strategy for mapping the covalent ligandability of primary brain cells freshly isolated from mice. By investigating sets of stereochemically defined electrophilic small molecules ("stereoprobes"), we identify liganding events for diverse proteins, including many with nervous system-enriched expression profiles. In this category were multiple hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which we show are covalently liganded by tryptoline acrylamide stereoprobes at a conserved cysteine in their cyclic nucleotide-binding domain. The stereoprobes were found to block cAMP-dependent shifts in voltage dependence while sparing basal HCN channel activity. Our work describes an advanced ABPP platform for identifying ligands targeting nervous system-enriched proteins, including chemical probes for modulating HCN channel function in cells. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-08-26 |
| AnnouncementXML | Submission_2026-08-26_08:51:56.405.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Elva Ye |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090; |
| ModificationList | iodoacetamide derivatized residue |
| Instrument | Orbitrap Eclipse; Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2026-08-20 20:59:29 | ID requested | |
| ⏵ 1 | 2026-08-26 08:51:57 | announced | |
Publication List
Keyword List
| submitter keyword: covalent ligandability, tryptoline acrylamide, cyclic nucleotide signaling, chemical proteomics, ligand discovery, HCN channels,Activity-based protein profiling, primary brain cells |
Contact List
| Benjamin Cravatt |
|---|
| contact affiliation | Department of Chemistry, Scripps Research |
| contact email | cravatt@scripps.edu |
| lab head | |
| Elva Ye |
|---|
| contact affiliation | Scripps Research |
| contact email | eye@scripps.edu |
| dataset submitter | |
Full Dataset Link List
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/2026/08/PXD082934 |
| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD082934
- Label: PRIDE project
- Name: Activity-based profiling of primary brain cells identifies covalent allosteric modulators of HCN channels
