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PMID: 17289572 Published · ppublish English Journal Article

Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex.

Cell ·Vol. 128 ·No. 3 ·2007-02-09 ·Pages 533-46

Park HH, Logette E, Raunser S, Cuenin S, Walz T, Tschopp J, Wu H

Abstract

Proteins of the death domain (DD) superfamily mediate assembly of oligomeric signaling complexes for the activation of caspases and kinases via unknown mechanisms. Here we report the crystal structure of the PIDD DD and RAIDD DD complex, which forms the core of the caspase-2-activating complex PIDDosome. Although RAIDD DD and PIDD DD are monomers, they assemble into a complex that comprises seven RAIDD DDs and five PIDD DDs. Despite the use of an asymmetric assembly mechanism, all DDs in the complex are in quasi-equivalent environments. The structure provided eight unique asymmetric interfaces, which can be classified into three types. These three types of interactions together cover a majority of the DD surface. Mutagenesis on almost all interfaces leads to disruption of the assembly, resulting in defective caspase-2 activation. The three types of interactions may represent most, if not all, modes of interactions in the DD superfamily for assembling complexes of different stoichiometry.

MeSH Terms
Amino Acid Sequence CRADD Signaling Adaptor Protein/chemistry,genetics,metabolism Caspase 2/metabolism Crystallography, X-Ray Death Domain Receptor Signaling Adaptor Proteins/chemistry,genetics,metabolism Models, Molecular Molecular Sequence Data Multiprotein Complexes/metabolism Mutagenesis, Site-Directed Protein Conformation Protein Structure, Tertiary Recombinant Proteins/chemistry,genetics,metabolism
Chemicals
CRADD Signaling Adaptor Protein Death Domain Receptor Signaling Adaptor Proteins Multiprotein Complexes Recombinant Proteins Caspase 2
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Park Hyun Ho
Weill Medical College, Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
Logette Emmanuelle
Raunser Stefan
Cuenin Solange
Walz Thomas
Tschopp Jurg
Wu Hao
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/j.cell.2007.01.019
Published
2007-02-09
Pages
533-46
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2908332
Subset
IM
Grants
NIAID NIH HHS · R01 AI050872 · United States
NIAID NIH HHS · R01 AI050872-06A1 · United States
Databases
PDB
2OF5
External Links
PubMed source DOI: 10.1016/j.cell.2007.01.019 PMC Full Text View journal details
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