Interleukin-1 f3-converting enzyme (ICE) proteolytically cleaves pro-IL-1 3 to its mature, active form. The crystal structure at 2.5 A resolution of a recombinant human ICE-tetrapeptide chloromethylketone 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 p10 in each domain suggests two alternative pathways of assembly and activation in vivo. ICE is homologous to the C. elegans cell death gene product, CED-3, and these may represent a novel class of cytoplasmic cysteine proteases that are important in programmed cell death (apoptosis). Conservation among members of the ICEICED-family of the amino acids that form the active site region of ICE sup ports the hypothesis that they share functional similarities.

Interleukin-1@ converting enzyme (ICE) is an unusual cytopiasmic cysteine protease that was first isolated from cells of monocyticorigin (Blacket al., 1966; Kosturaet al., 1969; Sieath et al., 1990; Howard et al., 1991). It cleaves at the Asp-l 16-Ala-117 bond in the inactive intracellular precursor for interleukin-18 (pro-IL-18) to generate the biologically active form of the cytokine. Two groups have cloned cDNAs for human ICE and found that it is not related to previously known proteases (Cerretti et al., 1992; Thornberry et al., 1992). The recent discovery that the product of the Caenorhabditis eiegans cell death gene ted-3 is similar in sequence to ICE suggests the intriguing possibility that there may be a family of cytopiasmic proteases