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环核苷酸门控通道孔内残基的暴露:门控过程中的P区结构与功能

Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating.

作者信息

Sun Z P, Akabas M H, Goulding E H, Karlin A, Siegelbaum S A

机构信息

Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.

出版信息

Neuron. 1996 Jan;16(1):141-9. doi: 10.1016/s0896-6273(00)80031-8.

DOI:10.1016/s0896-6273(00)80031-8
PMID:8562078
Abstract

In voltage-gated ion channels and in the homologous cyclic nucleotide-gated (CNG) channels, the loop between the S5 and S6 transmembrane segments (P region) is thought to form the lining of the pore. To investigate the structure and the role in gating of the P region of the bovine retinal CNG channel, we determined the accessibility of 11 cysteine-substituted P region residues to small, charged sulfhydryl reagents applied to the inside and outside of membrane patches in the open and closed states of the channel. The results suggest that the P region forms a loop that extends toward the central axis of the channel, analogous to the L3 loop of bacterial porin channels. Furthermore, the P region, in addition to forming the ion selectivity filter, functions as the channel gate, the structure of which changes when the channel opens.

摘要

在电压门控离子通道和同源环核苷酸门控(CNG)通道中,S5和S6跨膜片段之间的环(P区)被认为形成了孔道的内衬。为了研究牛视网膜CNG通道P区的结构及其在门控中的作用,我们测定了11个半胱氨酸取代的P区残基对应用于通道开放和关闭状态下膜片内外的带电荷小巯基试剂的可及性。结果表明,P区形成一个朝向通道中心轴延伸的环,类似于细菌孔蛋白通道的L3环。此外,P区除了形成离子选择性过滤器外,还作为通道门发挥作用,通道开放时其结构会发生变化。

相似文献

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Exposure of residues in the cyclic nucleotide-gated channel pore: P region structure and function in gating.环核苷酸门控通道孔内残基的暴露:门控过程中的P区结构与功能
Neuron. 1996 Jan;16(1):141-9. doi: 10.1016/s0896-6273(00)80031-8.
2
Change of pore helix conformational state upon opening of cyclic nucleotide-gated channels.环核苷酸门控通道开放时孔螺旋构象状态的变化。
Neuron. 2000 Dec;28(3):899-909. doi: 10.1016/s0896-6273(00)00162-8.
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A cysteine scan of the inner vestibule of cyclic nucleotide-gated channels reveals architecture and rearrangement of the pore.对环核苷酸门控通道内前庭进行的半胱氨酸扫描揭示了孔道的结构和重排。
J Gen Physiol. 2003 Jun;121(6):563-82. doi: 10.1085/jgp.200308819.
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Conformational changes in S6 coupled to the opening of cyclic nucleotide-gated channels.S6中的构象变化与环核苷酸门控通道的开放相关联。
Neuron. 2001 Jun;30(3):689-98. doi: 10.1016/s0896-6273(01)00324-5.
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Cyclic nucleotide-gated channels. Pore topology studied through the accessibility of reporter cysteines.环核苷酸门控通道。通过报告半胱氨酸的可及性研究孔道拓扑结构。
J Gen Physiol. 1999 Sep;114(3):377-92. doi: 10.1085/jgp.114.3.377.
6
Structural and functional determinants in the S5-P region of HCN-encoded pacemaker channels revealed by cysteine-scanning substitutions.通过半胱氨酸扫描替换揭示的HCN编码的起搏器通道S5-P区域的结构和功能决定因素。
Am J Physiol Cell Physiol. 2008 Jan;294(1):C136-44. doi: 10.1152/ajpcell.00340.2007. Epub 2007 Nov 7.
7
Cyclic nucleotide-gated channels: intra- and extracellular accessibility to Cd2+ of substituted cysteine residues within the P-loop.环核苷酸门控通道:P 环内取代半胱氨酸残基对 Cd2+的细胞内和细胞外可及性。
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Molecular basis of charge movement in voltage-gated sodium channels.电压门控钠通道中电荷移动的分子基础。
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Identification of channel-lining residues in the M2 membrane-spanning segment of the GABA(A) receptor alpha1 subunit.γ-氨基丁酸A(GABA(A))受体α1亚基M2跨膜片段中通道内衬残基的鉴定
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Localization of the activation gate for small conductance Ca2+-activated K+ channels.小电导钙激活钾通道激活门的定位
J Neurosci. 2002 Aug 1;22(15):6499-506. doi: 10.1523/JNEUROSCI.22-15-06499.2002.

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