Evolution-inspired redesign of the LPS receptor caspase-4 into an interleukin-1β converting enzyme.

ABSTRACT: Innate immune signaling pathways comprise multiple proteins that promote inflammation. This multistep means of information transfer suggests that complexity is a prerequisite for pathway design. Herein, we test this hypothesis by studying caspases that regulate inflammasome-dependent inflammation. Several caspases differ in their ability to recognize bacterial LPS and cleave interleukin-1β (IL-1β). No caspase is known to contain both activities, yet distinct caspases with complementary activities bookend an LPS-induced pathway to IL-1β cleavage. Using caspase-1/4 hybrid proteins present in canines as a guide, we identified molecular determinants of IL-1β cleavage specificity within caspase-1. This knowledge enabled the redesign of human caspase-4 to operate as a one-protein signaling pathw

SUBMITTER: Devant P 

PROVIDER: S-EPMC8559778 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature