title: Crystal structure of RAIDD death domain implicates potential mechanism of PIDDosome assembly.
abstract: Caspase-2 is implicated in stress-induced apoptosis that acts as an upstream initiator of mitochondrial permeabilization. Recent studies have shown that caspase-2 activation requires a molecular complex known as the PIDDosome comprising the p53-inducible protein PIDD, the adapter protein RAIDD and caspase-2. RAIDD has an N-terminal caspase recruitment domain (CARD) that interacts with the CARD of caspase-2 and a C-terminal death domain (DD) that interacts with the DD in PIDD. As a first step towards elucidating the molecular mechanisms of caspase-2 activation, we report the crystal structure of RAIDD DD at 2.0 A resolution. The high-resolution structure reveals important features of RAIDD DD that may be important for DD folding and dynamics and for assembly of the PIDDosome.
authors.affiliation: Department of Biochemistry, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053420:CRADD Signaling Adaptor Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D053143:Caspase 2; D020169:Caspases / Q000378:metabolism; D018360:Crystallography, X-Ray; D053418:Death Domain Receptor Signaling Adaptor Proteins; D004789:Enzyme Activation; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053420:CRADD Signaling Adaptor Protein; C104252:CRADD protein, human; D002352:Carrier Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D046912:Multiprotein Complexes; C485896:PIDD1 protein, human; D053143:Caspase 2; D020169:Caspases