The B30.2 domain of pyrin, the familial mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production

Abstract

Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder with high carrier frequencies in the Middle East. Pyrin, the protein mutated in FMF, regulates caspase-1 activation and consequently IL-1β production through cognate interaction of its N-terminal PYRIN motif with the ASC adaptor protein. However, the preponderance of mutations reside in pyrin's C-terminal B30.2 domain. Here we demonstrate direct interaction of this domain with caspase-1. In lysates from cells not expressing ASC, reciprocal GST pull-downs demonstrated the interaction of pyrin with the p20 and p10 catalytic subunits of caspase-1. Coimmunoprecipitations of pyrin and caspase-1 from THP-1 huma..