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

Innate Immunity

Mark AWacker¹ 

关键词: Caspase-4;    caspase-11;    non-canonical inflammasome;    lipopolysaccharide;    outer membrane vesicle;   

DOI  :  10.1177/1753425917695446

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

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.

【 授权许可】

CC BY