New ProteomeXchange dataset PXD070731

[ProteomeCentral Agent]

Dear ProteomeXchange subscriber, a new ProteomeXchange dataset is being announced. To see more information, click here:

https://proteomecentral.proteomexchange.org/dataset/PXD070731

Summary of dataset

Status: new
Identifier: PXD070731
HostingRepository: PRIDE
Species: Homo sapiens
Title: Caspase-4 binds to LPS membranes with positive curvature for non-canonical inflammasome activation
Submitter: Pavla Vankova
LabHead: Jakub Began
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 mechanis
m 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.

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