title: Homology modeling provides insights into the binding mode of the PAAD/DAPIN/pyrin domain, a fourth member of the CARD/DD/DED domain family.
abstract: The PAAD/DAPIN/pyrin domain is the fourth member of the death domain superfamily, but unlike other members of this family, it is involved not only in apoptosis but also in innate immunity and several other processes. We have identified 40 PAAD domain-containing proteins by extensively searching the genomes of higher eukaryotes and viruses. Phylogenetic analyses suggest that there are five categories of PAAD domains that correlate with the domain architecture of the entire proteins. Homology models built on CARD and DD structures identified functionally important residues by studying conservation patterns on the surface of the models. Surface maps of each subfamily show different distributions of these residues, suggesting that domains from different subfamilies do not interact with each other, forming independent regulatory networks. Helix3 of PAAD is predicted to be critical for dimerization. Multiple alignment analysis and modeling suggest that it may be partly disordered, following a new paradigm for interaction proteins that are stabilized by protein-protein interactions.
authors.affiliation: The Burnham Institute, La Jolla, California 92037, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Ana
authors.initials: A
authors.lastname: Rojas
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Ye
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D053468:CARD Signaling Adaptor Proteins; D017124:Conserved Sequence; D003459:Crystallins; D003598:Cytoskeletal Proteins / Q000737:chemistry; D006801:Humans; D008565:Membrane Proteins; D026901:Membrane Transport Proteins / Q000737:chemistry; D008958:Models, Molecular; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D000071198:Pyrin; D017386:Sequence Homology, Amino Acid
chemical_list: D053468:CARD Signaling Adaptor Proteins; C105445:CRYBG1 protein, human; D003459:Crystallins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C402202:PYCARD protein, human; D011506:Proteins; D000071198:Pyrin