Interaction of the aromatics Tyr-72/Trp-288 in the interface of the extracellular and transmembrane domains is essential for proton gating of acid-sensing ion channels.
Interaction of the aromatics Tyr-72/Trp-288 in the interface of the extracellular and transmembrane domains is essential for proton gating of acid-sensing ion channels.
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DOI：
10.1074/jbc.m805302200
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发表时间：
2009-02-13
影响因子：
4.8
通讯作者：
Canessa, Cecilia M.
中科院分区：
文献类型：
--
作者：
Li, Tianbo;Yang, Youshan;Canessa, Cecilia M.
酸敏感离子通道是在神经系统中表达的质子激活离子通道。它们属于ENaC/变性蛋白家族，其成员具有保守的结构，但被广泛不同的刺激激活。我们表明，两个芳香族残基，酪氨酸-72，位于第一个跨膜段后立即，和色氨酸-288，位于一个环的细胞外结构域的尖端指向第一个跨膜段的相互作用，是必不可少的质子激活的酸敏感离子通道。 含有Trp-288的亚结构域是通过短接头和假定的“质子传感器”中残基之间的亚基内相互作用拴系到胞外结构域的其余部分的模块。这两个区域的突变使质子的表观亲和力向更酸性的范围移动，并改变激活和脱敏的动力学。这些结果与模块相对于胞外结构域的其余部分的位移一致，以允许Trp-288与Tyr-72在门控期间相互作用。我们建议，这种相互作用可以提供功能性耦合之间的细胞外结构域和孔结构域。
Acid-sensing ion channels are proton-activated ion channels expressed in the nervous system. They belong to the family of ENaC/Degenerins whose members share a conserved structure but are activated by widely diverse stimuli. We show that interaction of two aromatic residues, Tyr-72, located immediately after the first transmembrane segment, and Trp-288, located at the tip of a loop of the extracellular domain directed toward the first transmembrane segment, is essential for proton activation of the acid-sensing ion channels. The subdomain containing Trp-288 is a module tethered to the rest of the extracellular domain by short linkers and intrasubunit interactions between residues in the putative “proton sensor.” Mutations in these two areas shift the apparent affinity of protons toward a more acidic range and change the kinetics of activation and desensitization. These results are consisting with displacement of the module relative to the rest of the extracellular domain to allow interaction of Trp-288 with Tyr-72 during gating. We propose that such interaction may provide functional coupling between the extracellular domain and the pore domain.