Homology modeling provides insights into the binding mode of the PAAD/DAPIN/pyrin domain, a fourth member of the CARD/DD/DED domain family
Homology modeling provides insights into the binding mode of the PAAD/DAPIN/pyrin domain, a fourth member of the CARD/DD/DED domain family
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DOI：
10.1110/ps.0359603
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发表时间：
2003-09-01
期刊：
影响因子：
8
通讯作者：
Godzik, A
中科院分区：
文献类型：
--
作者：
Liu, T;Rojas, A;Godzik, A
PAAD/DAPIN/pyrin结构域是死亡结构域超家族的第四个成员，但与该家族的其他成员不同，它不仅参与细胞凋亡，还参与先天免疫和其他几个过程。通过对高等真核生物和病毒基因组的广泛搜索，我们已经鉴定出40种含PAAD结构域的蛋白。系统发育分析表明，有五种类型的PAAD结构域与整个蛋白质的结构域结构相关。在CARD和DD结构上建立的同源模型通过研究模型表面的守恒模式来识别重要的功能残基。每个亚族的表面图谱显示出这些残基的不同分布，表明不同亚族的结构域不相互作用，形成独立的调控网络。预计PAAD的螺旋3对二聚化至关重要。多重比对分析和建模表明，它可能是部分无序的，遵循相互作用蛋白通过蛋白质相互作用稳定的新范式。
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.