Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism

Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic and extrinsic danger signals, and trigger inflammatory responses and pyroptotic cell death. Homotypic interactions among Pyrin domains and caspase recruitment domains (CARDs) in inflammasome-complex components mediate oligomerization into filamentous assemblies. Several cytosolic proteins consisting of only interaction domains exert inhibitory effects on inflammasome assembly. In this study, we determined the structure of the human caspase-1 CARD domain (caspase-1[superscript CARD]) filament by cryo-electron microscopy and investigated the biophysical properties of two caspase-1-like CARD-only proteins: human inhibitor of CARD (INCA or CARD17) and ICEBERG (CARD18). Our results reveal that INCA caps caspase-1 filaments, thereby exerting potent inhibition with low-nanomolar K[subscript i] on caspase-1[superscript CARD] polymerization in vitro and inflammasome activation in cells. Whereas caspase-1[superscript CARD] uses six complementary surfaces of three types for filament assembly, INCA is defective in two of the six interfaces and thus terminates the caspase-1 filament

A REVIEW ON THE EFFECTS OF SOME SELECTED PYRETHROIDS AND RELATED AGROCHEMICALS ON AQUATIC VERTEBRATE BIODIVERSITY

ABSTRACT Pollution in the aquatic ecosystem by pesticides, their metabolites and by-products is considered critical in the conservation of biodiversity and natural resources. Several studies have reported the toxicological issues and adverse effects of pesticides in aquatic biodiversity. After the development of the field ecotoxicology, researchers have expanded their studies towards the effects of pesticides in aquatic ecosystems. Pesticides containing chemicals such as Pyrethroids, cypermethrin, deltamethrin, cyphenothrin and other related compounds have been shown to cause adverse effects on the development, behaviour and mortality of different species of fish, birds, amphibians and aquatic mammals. This review article summarizes the adverse impact of the use of pesticides and related agrochemicals in populations of aquatic, amphibian and avian species