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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/33688

Title: The FIIND Domain of Nlrp1b Promotes Oligomerization and Pro-caspase-1 Activation in Response to Lethal Toxin of Bacillus anthracis
Authors: Joag, Vineet
Advisor: Mogridge, Jeremy
Department: Laboratory Medicine and Pathobiology
Keywords: Nlrp1b
FIIND domain
anthrax
lethal toxin
caspase-1
inflammasome
anthracis
pyroptosis
Issue Date: 29-Nov-2012
Abstract: Lethal toxin (LeTx) of Bacillus anthracis kills murine macrophages in a caspase-1 and Nod-like-receptor-protein 1b (Nlrp1b)-dependent manner. Nlrp1b detects intoxication, and self-associates to form a macromolecular complex called the inflammasome, which activates the pro-caspase-1 zymogen. I heterologously reconstituted the Nlrp1b inflammasome in human fibroblasts to characterize the role of the FIIND domain of Nlrp1b in pro-caspase-1 activation. Amino-terminal truncation analysis of Nlrp1b revealed that Nlrp1b1100-1233, containing the CARD domain and amino-terminal 42 amino acids within the FIIND domain was the minimal region that self-associated and activated pro-caspase-1. Residues 1100EIKLQIK1106 within the FIIND domain were critical for self-association and pro-caspase-1 activation potential of Nlrp1b1100-1233, but not for binding to pro-caspase-1. Furthermore, residues 1100EIKLQIK1106 were critical for cell death and pro-caspase-1 activation potential of full-length Nlrp1b upon intoxication. These data suggest that after Nlrp1b senses intoxication, the FIIND domain promotes self-association of Nlrp1b, which activates pro-caspase-1 zymogen due to induced pro-caspase-1 proximity.
URI: http://hdl.handle.net/1807/33688
Appears in Collections:Master

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