PXD070731

PXD070731 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-14 05:54:17	ID requested
⏵ 1	2026-03-09 18:09:42	announced

10.1016/J.IMMUNI.2025.12.017;

submitter keyword: caspase-4,Immunology, lipopolysaccharide sensing, host-pathogen interaction GBP1, membrane curvature, Inflammasomes

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

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/2026/03/PXD070731

PRIDE project URI

• PRIDE
  1. PXD070731
     1. Label: PRIDE project
     2. Name: Caspase-4 binds to LPS membranes with positive curvature for non-canonical inflammasome activation