C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating.
C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating.
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DOI：
10.1085/jgp.113.1.17
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发表时间：
1999-01
影响因子：
3.8
通讯作者：
Siegelbaum, SA
中科院分区：
文献类型：
--
作者：
Paoletti, P;Young, EC;Siegelbaum, SA
环核苷酸门控通道由结构上与电压门控K+通道同源的核心跨膜结构域和细胞质配体结合结构域组成。这两个模块由1090个保守氨基酸C-接头连接，其在环核苷酸通道激活机制中的确切作用知之甚少。我们研究了牛光感受器和秀丽隐杆线虫感觉神经元的环核苷酸门控通道，这些通道在环核苷酸的功效和敏感性方面存在显着差异。通过从这两个通道构建嵌合体，我们确定了C接头中的30个氨基酸区域（L2区域）作为激活特性的重要决定因素。通过用C区的L2区替换光感受器通道的L2区，可以使光感受器通道的门控功效和对cGMP和cAMP的表观亲和力增加。埃莱甘斯海峡该区域内的三个残基在很大程度上解释了这种效应。尽管C-接头区域对配体门控有深远的影响，但C-接头的身份不影响自发的、配体非依赖性的开放概率。基于活化的环状变构模型，我们提出C-接头将跨膜核心区的开放反应与激动剂开放通道亲和力的增强相结合，这是配体门控的基础。
Cyclic nucleotide–gated channels are composed of a core transmembrane domain, structurally homologous to the voltage-gated K+ channels, and a cytoplasmic ligand-binding domain. These two modules are joined by ∼90 conserved amino acids, the C-linker, whose precise role in the mechanism of channel activation by cyclic nucleotides is poorly understood. We examined cyclic nucleotide–gated channels from bovine photoreceptors and Caenorhabditis elegans sensory neurons that show marked differences in cyclic nucleotide efficacy and sensitivity. By constructing chimeras from these two channels, we identified a region of 30 amino acids in the C-linker (the L2 region) as an important determinant of activation properties. An increase in both the efficacy of gating and apparent affinity for cGMP and cAMP can be conferred onto the photoreceptor channel by the replacement of its L2 region with that of the C. elegans channel. Three residues within this region largely account for this effect. Despite the profound effect of the C-linker region on ligand gating, the identity of the C-linker does not affect the spontaneous, ligand-independent open probability. Based on a cyclic allosteric model of activation, we propose that the C-linker couples the opening reaction in the transmembrane core region to the enhancement of the affinity of the open channel for agonist, which underlies ligand gating.
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影响因子：
16.2
作者：
GOULDING, EH;NGAI, J;CHESS, A
通讯作者：
CHESS, A
影响因子：
64.8
作者：
GOULDING, EH;TIBBS, GR;SIEGELBAUM, SA
通讯作者：
SIEGELBAUM, SA
影响因子：
16.2
作者：
Liu, Y;Holmgren, M;Yellen, G
通讯作者：
Yellen, G
影响因子：
64.8
作者：
Gauss, R;Seifert, R;Kaupp, UB
通讯作者：
Kaupp, UB
影响因子：
16.2
作者：
KRAMER, RH;GOULDING, E;SIEGELBAUM, SA
通讯作者：
SIEGELBAUM, SA