High-affinity caspase-4 binding to LPS presented as high molecular mass aggregates or in outer membrane vesicles

Mark A Wacker; Athmane Teghanemt; Jerrold P Weiss; Jason H Barker

doi:10.1177/1753425917695446

Back

High-affinity caspase-4 binding to LPS presented as high molecular mass aggregates or in outer membrane vesicles

Journal article

Open access

Peer reviewed

High-affinity caspase-4 binding to LPS presented as high molecular mass aggregates or in outer membrane vesicles

Mark A Wacker, Athmane Teghanemt, Jerrold P Weiss and Jason H Barker

Innate immunity (London, England), Vol.23(4), pp.336-344

05/2017

DOI: 10.1177/1753425917695446

PMCID: PMC5540323

PMID: 28409545

Files and links (1)

url

https://doi.org/10.1177/1753425917695446View

Published (Version of record) Open Access

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.

Humans

Protein Multimerization

Lipopolysaccharides - metabolism

Recombinant Proteins - genetics

Caspases, Initiator - genetics

Mitochondrial Membranes - metabolism

Neisseria meningitidis - immunology

Protoplasts - metabolism

Caspases, Initiator - metabolism

Cell Wall - metabolism

Cytoplasmic Vesicles - metabolism

Protein Binding

Staphylococcus aureus - immunology

Details

Title: Subtitle: High-affinity caspase-4 binding to LPS presented as high molecular mass aggregates or in outer membrane vesicles
Creators: Mark A Wacker - 1 Department of Biology, Central Michigan University, Mt. Pleasant, MI, USA
Athmane Teghanemt - 3 Department of Internal Medicine, University of Iowa, and Iowa City VA Health Care System, Iowa City, IA, USA
Jerrold P Weiss - 4 Department of Microbiology, University of Iowa, and Iowa City VA Health Care System, Iowa City, IA, USA
Jason H Barker - 4 Department of Microbiology, University of Iowa, and Iowa City VA Health Care System, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Innate immunity (London, England), Vol.23(4), pp.336-344
DOI: 10.1177/1753425917695446
PMID: 28409545
PMCID: PMC5540323
ISSN: 1753-4259
eISSN: 1753-4267
Grant note: P01 AI044642 / NIAID NIH HHS R01 AI104728 / NIAID NIH HHS
Language: English
Date published: 05/2017
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094531802771

Metrics

15 Record Views

31 Times Cited - Web of Science

See more details