PXD070731 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Caspase-4 binds to LPS membranes with positive curvature for non-canonical inflammasome activation |
| Description | The non-canonical inflammasome, consisting of caspase-4 in humans, initiates pyroptosis upon detecting cytosolic lipopolysaccharide (LPS) from Gram-negative bacteria. For its activation, caspase-4 binds the hydrophobic, membrane-embedded lipid A moiety of LPS, but how it accesses lipid A remains unknown. Caspase-4 activation additionally requires guanylate-binding proteins (GBPs), which target the surface of cytosolic bacteria. Here, we report that GBP1 functions as a mechanoenzyme that can deform the LPS-containing outer membrane of bacteria in infected cells, or fragment tubular LPS micelles in vitro. GBP1-induced fragmentation improves the binding of caspase-4 to LPS micelles, mediated by a hydrophobic pocket within caspase-4-CARD, and thereby promotes LPS-induced caspase-4 activation. Finally, we find that caspase-4 specifically binds the tips of LPS micelles, i.e. regions with positive membrane curvature, for its activation. In summary, we propose a unified mechanism for the non-canonical inflammasome, in which GBP-mediated deformation of LPS membranes creates regions of positive curvature that allow caspase-4 to access lipid A, thereby driving caspase oligomerization and activation. |
| HostingRepository | PRIDE |
| AnnounceDate | 2026-03-10 |
| AnnouncementXML | Submission_2026-03-09_18:09:41.983.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Pavla Vankova |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | timsTOF Pro |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2025-11-14 05:54:17 | ID requested | |
| ⏵ 1 | 2026-03-09 18:09:42 | announced | |
Publication List
Keyword List
| submitter keyword: caspase-4,Immunology, lipopolysaccharide sensing, host-pathogen interaction GBP1, membrane curvature, Inflammasomes |
Contact List
| Jakub Began |
|---|
| contact affiliation | Department of Immunobiology, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland |
| contact email | jakub.began@unil.ch |
| lab head | |
| Pavla Vankova |
|---|
| contact affiliation | Institute of Biotechnology of the Czech Academy of Sciences, BioCeV, Prumyslova 595, 252 50 Vestec, Czech Republic |
| contact email | pavla.vankova@ibt.cas.cz |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD070731
- Label: PRIDE project
- Name: Caspase-4 binds to LPS membranes with positive curvature for non-canonical inflammasome activation
