Document Detail

Death domain assembly mechanism revealed by crystal structure of the oligomeric PIDDosome core complex.
MedLine Citation:
PMID:  17289572     Owner:  NLM     Status:  MEDLINE    
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.
Hyun Ho Park; Emmanuelle Logette; Stefan Raunser; Solange Cuenin; Thomas Walz; Jurg Tschopp; Hao Wu
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell     Volume:  128     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-09     Completed Date:  2007-03-28     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  533-46     Citation Subset:  IM    
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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
Grant Support
Reg. No./Substance:
0/CRADD Signaling Adaptor Protein; 0/Death Domain Receptor Signaling Adaptor Proteins; 0/Multiprotein Complexes; 0/Recombinant Proteins; EC 3.4.22.-/Caspase 2

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