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

Cell. 1994 Jul 29;78(2):343-52. doi: 10.1016/0092-8674(94)90303-4.

Abstract

Interleukin-1 beta-converting enzyme (ICE) proteolytically cleaves pro-IL-1 beta 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 ICE/CED-3 family of the amino acids that form the active site region of ICE supports the hypothesis that they share functional similarities.

MeSH terms

  • 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*

Substances

  • Amino Acid Chloromethyl Ketones
  • Recombinant Proteins
  • Serpins
  • Viral Proteins
  • interleukin-1beta-converting enzyme inhibitor