Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10) 2 homodimer

• Published in: Cell Vol. 78; no. 2; pp. 343 - 352
• Main Authors: Walker, N.P.C., Talanian, R.V., Brady, K.D., Dang, L.C., Bump, N.J., Ferenza, C.R., Franklin, S., Ghayur, T., Hackett, M.C., Hammill, L.D., Herzog, L., Hugunin, M., Houy, W., Mankovich, J.A., McGuiness, L., Orlewicz, E., Paskind, M., Pratt, C.A., Reis, P., Summani, A., Terranova, M., Welch, J.P., Xiong, L., Möller, A., Tracey, D.E., Kamen, R., Wong, W.W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.07.1994
• Subjects: Amino Acid Chloromethyl Ketones - metabolism; Amino Acid Sequence; Apoptosis; Crystallization; Crystallography, X-Ray; Humans; Models, Molecular; Molecular Sequence Data; Molecular Structure; Protein Binding; Protein Conformation; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Sequence Alignment; Sequence Homology, Amino Acid; Serpins - chemistry; Serpins - genetics; Serpins - metabolism; Viral Proteins
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/0092-8674(94)90303-4

Interleukin-1β-converting enzyme (ICE) proteolytically cleaves pro-IL-1β to its mature, active form. The crystal structure at 2.5 Å 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 ICE/CED-3 family of the amino acids that form the active site region of ICE supports the hypothesis that they share functional similarities.