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- Title
High-affinity caspase-4 binding to LPS presented as high molecular mass aggregates or in outer membrane vesicles.
- Authors
Wacker, Mark A; Teghanemt, Athmane; Weiss, Jerrold P; Barker, Jason H
- 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 endotoxinrich 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.
- Subjects
CASPASES; VESICLES (Cytology); INFLAMMASOMES; ENDOTOXINS; TOLL-like receptors
- Publication
Innate Immunity, 2017, Vol 23, Issue 4, p336
- ISSN
1753-4259
- Publication type
Article
- DOI
10.1177/1753425917695446