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

Nigel P.C. Walker , Robert V. Talanian , Kenneth D. Brady , Nigel P.C. Walker , Robert V. Talanian , Kenneth D. Brady , Luan C. Dang , Nancy J. Bump , C.R. Ferenza , Simon Franklin , Tariq Ghayur , Maria Hackett , Linda Hammill , Linda Herzog , Margaret Hugunin , W. Houy , John A. Mankovich , L. McGuiness , E. Orlewicz , Michael Paskind , Clifford Pratt , Pablo Victor Mendes dos Reis , A. Summani , Michele Terranova , Jeffrey P. Welch , Xiong Lu , Abraham Moller , Daniel E. Tracey , Robert Kamen , W. Wei‐Lynn Wong
1994 Cell 569 citations

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.

Keywords

BiologyCysteine proteaseCysteineProteasesSerine proteaseSerineCaspaseTetrapeptideBiochemistryCell biologyAmino acidActive siteEnzymeC-terminusProgrammed cell deathProteasePeptideApoptosis

MeSH Terms

Amino Acid Chloromethyl KetonesAmino Acid SequenceApoptosisCrystallizationCrystallographyX-RayHumansModelsMolecularMolecular Sequence DataMolecular StructureProtein BindingProtein ConformationRecombinant ProteinsSequence AlignmentSequence HomologyAmino AcidSerpinsViral Proteins

Related Publications

Publication Info

Year
1994
Type
article
Volume
78
Issue
2
Pages
343-352
Citations
569
Access
Closed

External Links

Download PDF (Free) View on DOI.org PubMed Semantic Scholar

Social Impact

Altmetric
PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

569
OpenAlex
9
Influential
467
CrossRef

Cite This

Nigel P.C. Walker, Robert V. Talanian, Kenneth D. Brady et al. (1994). Crystal structure of the cysteine protease interleukin-1β-converting enzyme: A (p20/p10)2 homodimer. Cell , 78 (2) , 343-352. https://doi.org/10.1016/0092-8674(94)90303-4

Identifiers

DOI
10.1016/0092-8674(94)90303-4
PMID
8044845

Data Quality

Data completeness: 81%