High-affinity Caspase-4 Binding to LPS Presented As High Molecular Mass Aggregates or in Outer Membrane Vesicles

Overview

Journal Innate Immun

Publisher Sage Publications

Specialties Allergy & Immunology
Microbiology

Date 2017 Apr 15

PMID 28409545

Citations 21

Authors

Mark A Wacker

Athmane Teghanemt

Jerrold P Weiss

Jason H Barker

Affiliations

Soon will be listed here.

Abstract

Caspases of the non-canonical inflammasome (caspases -4, -5, and -11) directly bind endotoxin (LOS/LPS) and can be activated in the absence of any co-factors. Models of LPS-induced caspase activation have postulated that 1:1 binding of endotoxin monomers to caspase trigger caspase oligomerization and activation, analogous to that established for endotoxin-induced activation of MD-2/TLR4. However, using metabolically radiolabeled LOS and LPS, we now show high affinity and selective binding of caspase-4 to high molecular mass aggregates of purified endotoxin and to endotoxin-rich outer membrane vesicles without formation of 1:1 endotoxin:caspase complexes. Thus, our findings demonstrate markedly different endotoxin recognition properties of caspase-4 from that of MD-2/TLR4 and strongly suggest that activation of caspase-4 (and presumably caspase-5 and caspase-11) are mediated by interactions with activating endotoxin-rich membrane interfaces rather than by endotoxin monomers.

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