Structural basis of caspase inhibition by XIAP: Differential roles of the linker versus the BIR domain
Structural basis of caspase inhibition by XIAP: Differential roles of the linker versus the BIR domain
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DOI：
10.1016/s0092-8674(01)00273-2
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发表时间：
2001-03-09
期刊：
影响因子：
64.5
通讯作者：
Wu, H
中科院分区：
文献类型：
--
作者：
Huang, YH;Park, YC;Wu, H
凋亡抑制蛋白(IAP)是唯一的内源性caspase抑制蛋白，其特征是存在杆状病毒IAP重复序列(BIR)。在这里，我们报告了人caspase-7与XIAP(BIR2和随后的连接子)之间的复合物的晶体结构。结构令人惊讶地揭示了连接子是caspase唯一的接触元件，而BIR2结构域在晶体中是看不见的。与底物识别不同，接头以向后的方式与半胱氨酸天冬氨酸酶的底物凹槽相互作用并阻止。结构分析表明，连接子是相互作用的能量和特异性决定因素。进一步的生化特征清楚地表明，连接子含有主要的能量决定簇，而BIR2结构域则是caspase结合和Smac中和的调节元件。
The inhibitor of apoptosis proteins (IAPs) represent the only endogenous caspase inhibitors and are characterized by the presence of baculoviral IAP repeats (BIRs). Here, we report the crystal structure of the complex between human caspase-7 and XIAP (BIR2 and the proceeding linker). The structure surprisingly reveals that the linker is the only contacting element for the caspase, while the BIR2 domain is invisible in the crystal. The linker interacts with and blocks the substrate groove of the caspase in a backward fashion, distinct from substrate recognition. Structural analyses suggest that the linker is the energetic and specificity determinant of the interaction. Further biochemical characterizations clearly establish that the linker harbors the major energetic determinant, while the BIR2 domain serves as a regulatory element for caspase binding and Smac neutralization.