CRYSTAL-STRUCTURE OF THE CYSTEINE PROTEASE INTERLEUKIN-1-BETA-CONVERTING ENZYME - A (P20 P10)(2) HOMODIMER/

Interleukin-1 beta-converting enzyme (ICE) proteolytically cleaves pro -IL-1 beta to its mature, active form. The crystal structure at 2.5 An gstrom resolution of a recombinant human ICE-tetrapeptide chloromethyl ketone complex reveals that the holoenzyme is a homodimer of catalytic domains, each of which contains a p20 and a p10 subunit. The spatial separation of the C-terminus of p20 and the N-terminus of pin in each domain suggests two alternative pathways of assembly and activation in vivo. ICE is homologous to the C. elegans cell death gene product, CE D-3, and these may represent a novel class of cytoplasmic cysteine pro teases that are important in programmed cell death (apoptosis). Conser vation among members of the ICE/CED-3 family of the amino acids that f orm the active site region of ICE supports the hypothesis that they sh are functional similarities.