Department for Molecular Biomedical Research, VIB, B-9052 Ghent (Zwijnaarde), Belgium.
Trends Biochem Sci. 2011 Oct;36(10):541-52. doi: 10.1016/j.tibs.2011.06.006. Epub 2011 Jul 26.
The death-fold superfamily encompasses four structurally homologous subfamilies that engage in homotypic, subfamily-restricted interactions. The Death Domains (DDs), the Death Effector Domains (DEDs), the CAspase Recruitment Domains (CARDs) and the PYrin Domains (PYDs) constitute key building blocks involved in the assembly of multimeric complexes implicated in signaling cascades leading to inflammation and cell death. We review the molecular basis of these homotypic domain-domain interactions in light of their structure, function and evolution. In addition, we elaborate on three distinct types of asymmetric interactions that were recently identified from the crystal structures of three multimeric, death-fold complexes: the MyDDosome, the PIDDosome and the Fas/FADD-DISC. Insights into the mechanisms of interaction of death-fold domains will be useful to design strategies for specific modulation of complex formation and might lead to novel therapeutic applications.
死亡结构域超家族包含四个结构同源的亚家族，它们进行同型、亚家族特异性相互作用。死亡结构域 (DDs)、死亡效应结构域 (DEDs)、胱天蛋白酶募集结构域 (CARDs) 和 PYrin 结构域 (PYDs) 构成了参与组装多聚体复合物的关键构建块，这些复合物涉及到导致炎症和细胞死亡的信号级联反应。我们根据结构、功能和进化来回顾这些同型结构域-结构域相互作用的分子基础。此外，我们详细阐述了最近从三个多聚体死亡结构域复合物的晶体结构中鉴定出的三种不同类型的不对称相互作用：MyDDosome、PIDDosome 和 Fas/FADD-DISC。对死亡结构域相互作用机制的深入了解将有助于设计针对特定调节复合物形成的策略，并可能导致新的治疗应用。
