Crystal structure of RAIDD death domain implicates potential mechanism of PIDDosome assembly.
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.
Park
Hyun Ho
HH
Department of Biochemistry, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA.
Wu
Hao
H
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
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