Monomer/dimer transition of the caspase-recruitment domain of human Nod1.
Monomer/dimer transition of the caspase-recruitment domain of human Nod1.
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DOI：
10.1021/bi7016602
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发表时间：
2008-01
期刊：
影响因子：
2.9
通讯作者：
T. Srimathi;S. L. Robbins;R. L. Dubas;M. Hasegawa;N. Inohara;Y. Park
中科院分区：
文献类型：
--
作者：
T. Srimathi;S. L. Robbins;R. L. Dubas;M. Hasegawa;N. Inohara;Y. Park
Nod1是先天免疫系统中细菌肽聚糖的重要细胞质传感器。Nod1的caspase募集结构域（Nod1_CARD）对于募集下游激酶、受体相互作用蛋白2 （RIP2）是必不可少的，RIP2可以激活核因子- kappab （NF-kappaB）。人类Nod1_CARD在1.9 A分辨率下的晶体结构揭示了一种新的同型二聚体构象。我们的结构和生化分析表明，Nod1_CARD的同二聚化是通过交换羧基末端的H6螺旋实现的，并通过在溶液和晶体中两个单体的Cys39残基之间形成链间二硫键来稳定。此外，我们还提供了实验证据，证明Nod1_CARD具有ph敏感性构象变化。我们的研究结果表明，ph敏感性单体/二聚体转变是Nod1_CARD的独特分子性质。
Nod1 is an essential cytoplasmic sensor for bacterial peptidoglycans in the innate immune system. The caspase-recruitment domain of Nod1 (Nod1_CARD) is indispensable for recruiting a downstream kinase, receptor-interacting protein 2 (RIP2), that activates nuclear factor-kappaB (NF-kappaB). The crystal structure of human Nod1_CARD at 1.9 A resolution reveals a novel homodimeric conformation. Our structural and biochemical analysis shows that the homodimerization of Nod1_CARD is achieved by swapping the H6 helices at the carboxy termini and stabilized by forming an interchain disulfide bond between the Cys39 residues of the two monomers in solution and in the crystal. In addition, we present experimental evidence for a pH-sensitive conformational change of Nod1_CARD. Our results suggest that the pH-sensitive monomer/dimer transition is a unique molecular property of Nod1_CARD.