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基于八角形结构模型的钠通道功能

Sodium channel functioning based on an octagonal structure model.

作者信息

Sato C, Matsumoto G

机构信息

Electrotechnical Laboratory, Supermolecular Science Division, Ibaraki, Japan.

出版信息

J Membr Biol. 1995 Sep;147(1):45-70. doi: 10.1007/BF00235397.

DOI:10.1007/BF00235397
PMID:8531199
Abstract

The complete amino acid sequence of a sodium channel from squid Loligo bleekeri has been deduced by cloning and sequence analysis of the complementary DNA. A unique feature of the squid sodium channel is the 1,522 residue sequence, approximately three-fourths of those of the rat sodium channels I, II and III. On the basis of the sequence, and in comparison with those of vertebrate sodium channels, we have proposed a tertiary structure model of the sodium channel where the transmembrane segments are octagonally aligned and the four linkers of S5-6 between segments S5 and S6 play a crucial role in the activation gate, voltage sensor and ion selective pore, which can slide, depending on membrane potentials, along inner walls consisting of alternating segments S2 and S4. The proposed octagonal structure model is contrasted with that of Noda et al. (Nature 320; 188-192, 1986). The octagonal structure model can explain the gating of activation and inactivation, and ion selectivity, as well as the action mechanism of both tetrodotoxin (TTX) and alpha-scorpion toxin (ScTX), and can be applied not only to the sodium channel, but also to the calcium channel, potassium channel and cGMP-gated channel.

摘要

通过对鱿鱼(Loligo bleekeri)钠通道互补DNA的克隆和序列分析,推导得出了其完整的氨基酸序列。鱿鱼钠通道的一个独特特征是其1522个残基的序列,约为大鼠钠通道I、II和III序列的四分之三。基于该序列,并与脊椎动物钠通道的序列进行比较,我们提出了钠通道的三级结构模型,其中跨膜片段呈八边形排列,S5和S6片段之间的四个S5-6连接子在激活门、电压传感器和离子选择性孔中起关键作用,它们可根据膜电位沿着由交替的S2和S4片段组成的内壁滑动。所提出的八边形结构模型与野田等人(《自然》320;188 - 192,1986)的模型形成对比。该八边形结构模型能够解释激活和失活的门控、离子选择性,以及河豚毒素(TTX)和α - 蝎毒素(ScTX)的作用机制,并且不仅可应用于钠通道,还可应用于钙通道、钾通道和cGMP门控通道。

相似文献

1
Sodium channel functioning based on an octagonal structure model.基于八角形结构模型的钠通道功能
J Membr Biol. 1995 Sep;147(1):45-70. doi: 10.1007/BF00235397.
2
[Channel structure and functioning based on octagonal structure model].[基于八角结构模型的通道结构与功能]
Nihon Rinsho. 1996 Mar;54(3):744-56.
3
Proposed tertiary structure of the sodium channel.
Biochem Biophys Res Commun. 1992 Jul 31;186(2):1158-67. doi: 10.1016/0006-291x(92)90868-l.
4
Primary structure of squid sodium channel deduced from the complementary DNA sequence.从互补DNA序列推导的鱿鱼钠通道一级结构。
Biochem Biophys Res Commun. 1992 Jul 15;186(1):61-8. doi: 10.1016/s0006-291x(05)80775-2.
5
Molecular pore structure of voltage-gated sodium and calcium channels.电压门控钠通道和钙通道的分子孔结构
Braz J Med Biol Res. 1994 Dec;27(12):2781-802.
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Molecular cloning of a novel form (two-repeat) protein related to voltage-gated sodium and calcium channels.一种与电压门控钠通道和钙通道相关的新型(两重复)蛋白质的分子克隆
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Biochemistry. 2000 Jul 18;39(28):8161-70. doi: 10.1021/bi000486w.
8
[Sodium channel functioning based on an octagonal structure model].基于八角形结构模型的钠通道功能
Tanpakushitsu Kakusan Koso. 1995 Mar;40(4):370-88.
9
Mapping of scorpion toxin receptor sites at voltage-gated sodium channels.蝎毒素受体在电压门控钠离子通道上的定位。
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The S4-S5 linker couples voltage sensing and activation of pacemaker channels.S4-S5连接体将电压传感与起搏通道的激活相耦合。
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11277-82. doi: 10.1073/pnas.201250598. Epub 2001 Sep 11.

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