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Srimathi T , Robbins SL , Dubas RL , Hasegawa M , Inohara N , Park YC
Monomer/dimer transition of the caspase-recruitment domain of human Nod1
Biochemistry. 2008 Feb 5;47(5) :1319-25
PMID: 18186648   
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Abstract
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.
Notes
Srimathi, Thiagarajan Robbins, Sheila L Dubas, Rachel L Hasegawa, Mizuho Inohara, Naohiro Park, Young Chul Research Support, Non-U.S. Gov't United States Biochemistry Biochemistry. 2008 Feb 5;47(5):1319-25. Epub 2008 Jan 11.