Interdomain interactions underlying activation of cyclic nucleotide-gated channels
Interdomain interactions underlying activation of cyclic nucleotide-gated channels
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DOI：
10.1126/science.278.5335.110
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发表时间：
1997-10-03
期刊：
影响因子：
56.9
通讯作者：
Zagotta, WN
中科院分区：
文献类型：
--
作者：
Varnum, MD;Zagotta, WN
环核苷酸门控（CNG）离子通道是响应环核苷酸与细胞内结构域结合而激活的多聚体蛋白。本研究表明，大鼠嗅觉CNG通道的氨基末端结构域和羧基末端配体结合结构域之间的分子内蛋白-蛋白相互作用对通道激活具有自兴奋作用。在气味适应过程中调节CNG通道活性的钙-钙调蛋白阻断了这种相互作用。在体外实验中，氨基末端结构域的特异性缺失破坏了结构域间的相互作用，改变了表达通道的门控特性和钙调素敏感性。因此，氨基端结构域可以通过直接与羧基端门控机制相互作用来促进通道打开；钙调蛋白通过靶向这种相互作用来调节通道活性。
Cyclic nucleotide-gated (CNG) ion channels are multimeric proteins that activate in response to the binding of cyclic nucleotide to intracellular domains. Here, an intramolecular protein-protein interaction between the amino-terminal domain and the carboxylterminal ligand-binding domain of the rat olfactory CNG channel was shown to exert an autoexcitatory effect on channel activation. Calcium-calmodulin, which modulates CNG channel activity during odorant adaptation, blocked this interaction. A specific deletion within the amino-terminal domain disrupted the interdomain interaction in vitro and altered the gating properties and calmodulin sensitivity of expressed channels. Thus, the amino-terminal domain may promote channel opening by directly interacting with the carboxyl-terminal gating machinery; calmodulin regulates channel activity by targeting this interaction.