title: Analysis of mutation effects on PIDDosome core complex.
abstract: PIDDosome is a recently-identified caspase-2-activating molecular complex formed by genotoxic stress that leads to caspase-2-dependent apoptosis. PIDD, RAIDD, and caspase-2 are three protein components of PIDDosome. The core portion of PIDDosome is formed by the unique screw rotation of seven RAIDD DD and five PIDD DD. In the current study, we found that two mutations generated during structural-based mutagenesis studies, Q169E and R170A on RAIDD DD, were dominant negative. Because the discovery of dominant-negative mutants might implicate the disease and therapeutic intervention, newly identified dominant-negative mutants could lead to new potential applications for treatment of human diseases caused by excessive or reduced apoptosis.
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan, South Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Jang
authors.forename: En Kyung
authors.initials: EK
authors.lastname: Seo
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053420:CRADD Signaling Adaptor Protein / Q000737:chemistry* / Q000235:genetics; D053143:Caspase 2 / Q000737:chemistry* / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D053420:CRADD Signaling Adaptor Protein; C104252:CRADD protein, human; D053418:Death Domain Receptor Signaling Adaptor Proteins; C485896:PIDD1 protein, human; D011993:Recombinant Fusion Proteins; C490360:CASP2 protein, human; D053143:Caspase 2; D003546:Cysteine Endopeptidases