KcsA 质子依赖性门控的分子机制。
A molecular mechanism for proton-dependent gating in KcsA.
机构信息
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
出版信息
FEBS Lett. 2010 Mar 19;584(6):1126-32. doi: 10.1016/j.febslet.2010.02.003. Epub 2010 Feb 6.
Abstract
Activation gating in KcsA is elicited by changes in intracellular proton concentration. Thompson et al. identified a charge cluster around the inner gate that plays a key role in defining proton activation in KcsA. Here, through functional and spectroscopic approaches, we confirmed the role of this charge cluster and now provide a mechanism of pH-dependent gating. Channel opening is driven by a set of electrostatic interactions that include R117, E120 and E118 at the bottom of TM2 and H25 at the end of TM1. We propose that electrostatic compensation in this charge cluster stabilizes the closed conformation at neutral pH and that its disruption at low pH facilitates the transition to the open conformation by means of helix-helix repulsion.
摘要
激活门控在 KcsA 中是由细胞内质子浓度的变化引起的。Thompson 等人鉴定了内门周围的一个电荷簇，该电荷簇在定义 KcsA 中的质子激活中起着关键作用。在这里，我们通过功能和光谱学方法证实了这个电荷簇的作用，并提供了一个 pH 依赖性门控的机制。通道的开启是由一组静电相互作用驱动的，这些相互作用包括 TM2 底部的 R117、E120 和 E118 以及 TM1 末端的 H25。我们提出，这个电荷簇中的静电补偿稳定了中性 pH 下的关闭构象，而在低 pH 下的破坏则通过螺旋-螺旋排斥作用促进了向开放构象的转变。
相似文献
1
A molecular mechanism for proton-dependent gating in KcsA.KcsA 质子依赖性门控的分子机制。
FEBS Lett. 2010 Mar 19;584(6):1126-32. doi: 10.1016/j.febslet.2010.02.003. Epub 2010 Feb 6.
2
Design and characterization of a constitutively open KcsA.设计并鉴定一种组成型开放的 KcsA。
FEBS Lett. 2010 Mar 19;584(6):1133-8. doi: 10.1016/j.febslet.2010.02.015. Epub 2010 Feb 12.
3
Role of the KcsA channel cytoplasmic domain in pH-dependent gating.KcsA 通道胞质结构域在 pH 依赖性门控中的作用。
Biophys J. 2011 Nov 2;101(9):2157-62. doi: 10.1016/j.bpj.2011.09.024. Epub 2011 Nov 1.
4
Global twisting motion of single molecular KcsA potassium channel upon gating.门控时单个分子KcsA钾通道的整体扭转运动。
Cell. 2008 Jan 11;132(1):67-78. doi: 10.1016/j.cell.2007.11.040.
5
Investigation of a KcsA Cytoplasmic pH Gate in Lipoprotein Nanodiscs.脂蛋白纳米盘中的 KcsA 细胞质 pH 门控研究。
Chembiochem. 2019 Mar 15;20(6):813-821. doi: 10.1002/cbic.201800627. Epub 2019 Feb 5.
6
Molecular determinants of gating at the potassium-channel selectivity filter.钾通道选择性过滤器门控的分子决定因素。
Nat Struct Mol Biol. 2006 Apr;13(4):311-8. doi: 10.1038/nsmb1069. Epub 2006 Mar 12.
7
Structure of a KirBac potassium channel with an open bundle crossing indicates a mechanism of channel gating.具有开放束交叉的 KirBac 钾通道结构表明了通道门控的机制。
Nat Struct Mol Biol. 2012 Jan 8;19(2):158-63. doi: 10.1038/nsmb.2208.
8
Mechanism of activation gating in the full-length KcsA K+ channel.全长 KcsA K+ 通道激活门控的机制。
Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11896-9. doi: 10.1073/pnas.1105112108. Epub 2011 Jul 5.
9
Molecular interactions involved in proton-dependent gating in KcsA potassium channels.KcsA 钾通道中质子依赖门控涉及的分子相互作用。
J Gen Physiol. 2013 Dec;142(6):613-24. doi: 10.1085/jgp.201311057. Epub 2013 Nov 11.
10
Molecular mechanism of pH sensing in KcsA potassium channels.KcsA钾通道中pH感知的分子机制。
Proc Natl Acad Sci U S A. 2008 May 13;105(19):6900-5. doi: 10.1073/pnas.0800873105. Epub 2008 Apr 28.
引用本文的文献
1
Anionic Phospholipids Shift the Conformational Equilibrium of the Selectivity Filter in the KcsA Channel to the Conductive Conformation: Predicted Consequences on Inactivation.阴离子磷脂将KcsA通道中选择性过滤器的构象平衡转移至导电构象：对失活的预测结果。
Biomedicines. 2023 May 5;11(5):1376. doi: 10.3390/biomedicines11051376.
2
Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels.脊椎动物耳石蛋白质子通道的亚型特异性 pH 敏感性门控的结构基序。
Elife. 2022 Aug 3;11:e77946. doi: 10.7554/eLife.77946.
3
Structures of Gating Intermediates in a K channel.K 通道门控中间态的结构。
J Mol Biol. 2021 Nov 19;433(23):167296. doi: 10.1016/j.jmb.2021.167296. Epub 2021 Oct 8.
4
Tetraoctylammonium, a Long Chain Quaternary Ammonium Blocker, Promotes a Noncollapsed, Resting-Like Inactivated State in KcsA.四辛基铵，一种长链季铵阻断剂，促进 KcsA 形成非塌陷、类似静息失活状态。
Int J Mol Sci. 2021 Jan 6;22(2):490. doi: 10.3390/ijms22020490.
5
NMR studies of lipid regulation of the K channel KcsA.NMR 研究脂质对 KcsA 钾通道的调节作用。
Biochim Biophys Acta Biomembr. 2021 Mar 1;1863(3):183491. doi: 10.1016/j.bbamem.2020.183491. Epub 2020 Oct 13.
6
Probing allosteric coupling in a constitutively open mutant of the ion channel KcsA using solid-state NMR.利用固态 NMR 探测离子通道 KcsA 组成型开放突变体中的变构偶联。
Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7171-7175. doi: 10.1073/pnas.1908828117. Epub 2020 Mar 18.
7
Structure, function, and ion-binding properties of a K channel stabilized in the 2,4-ion-bound configuration.一种钾通道在 2,4-离子结合构象下稳定的结构、功能和离子结合特性。
Proc Natl Acad Sci U S A. 2019 Aug 20;116(34):16829-16834. doi: 10.1073/pnas.1901888116. Epub 2019 Aug 6.
8
Accessibility of Cations to the Selectivity Filter of KcsA in the Inactivated State: An Equilibrium Binding Study.失活态 KcsA 选择性过滤器中阳离子的可及性：平衡结合研究。
Int J Mol Sci. 2019 Feb 5;20(3):689. doi: 10.3390/ijms20030689.
9
Selective exclusion and selective binding both contribute to ion selectivity in KcsA, a model potassium channel.在典型的钾通道KcsA中，选择性排斥和选择性结合都对离子选择性有贡献。
J Biol Chem. 2017 Sep 15;292(37):15552-15560. doi: 10.1074/jbc.M117.795807. Epub 2017 Aug 4.
10
Activation of the mechanosensitive ion channel MscL by mechanical stimulation of supported Droplet-Hydrogel bilayers.受支持的液滴-水凝胶双层结构的机械刺激激活机械敏感离子通道 MscL。
Sci Rep. 2017 Mar 27;7:45180. doi: 10.1038/srep45180.
本文引用的文献
1
Design and characterization of a constitutively open KcsA.设计并鉴定一种组成型开放的 KcsA。
FEBS Lett. 2010 Mar 19;584(6):1133-8. doi: 10.1016/j.febslet.2010.02.015. Epub 2010 Feb 12.
2
Crystal structure of full-length KcsA in its closed conformation.处于关闭构象的全长KcsA的晶体结构。
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6644-9. doi: 10.1073/pnas.0810663106. Epub 2009 Apr 3.
3
Genetic selection of activatory mutations in KcsA.KcsA中激活突变的基因选择。
Channels (Austin). 2008 Nov-Dec;2(6):413-8. doi: 10.4161/chan.2.6.6874. Epub 2008 Nov 27.
4
Conformational changes in the selectivity filter of the open-state KcsA channel: an energy minimization study.开放态KcsA通道选择性过滤器的构象变化：能量最小化研究
Biophys J. 2008 Oct;95(7):3239-51. doi: 10.1529/biophysj.108.136556. Epub 2008 Jul 11.
5
Molecular mechanism of pH sensing in KcsA potassium channels.KcsA钾通道中pH感知的分子机制。
Proc Natl Acad Sci U S A. 2008 May 13;105(19):6900-5. doi: 10.1073/pnas.0800873105. Epub 2008 Apr 28.
6
Open-state conformation of the KcsA K+ channel: Monte Carlo normal mode following simulations.KcsA钾离子通道的开放态构象：模拟后的蒙特卡洛正常模式
Structure. 2007 Dec;15(12):1654-62. doi: 10.1016/j.str.2007.09.022.
7
Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a.参与酸敏感离子通道1a氢离子门控的候选氨基酸。
J Biol Chem. 2008 Jan 4;283(1):572-581. doi: 10.1074/jbc.M706811200. Epub 2007 Nov 1.
8
Conformational dynamics of the KcsA potassium channel governs gating properties.KcsA钾通道的构象动力学决定门控特性。
Nat Struct Mol Biol. 2007 Nov;14(11):1089-95. doi: 10.1038/nsmb1311. Epub 2007 Oct 7.
9
Identification and characterization of the slowly exchanging pH-dependent conformational rearrangement in KcsA.KcsA中缓慢交换的pH依赖性构象重排的鉴定与表征。
J Biol Chem. 2007 May 18;282(20):15179-86. doi: 10.1074/jbc.M608264200. Epub 2007 Mar 14.
10
Semisynthesis of a functional K+ channel.功能性钾通道的半合成
Angew Chem Int Ed Engl. 2004 May 3;43(19):2504-7. doi: 10.1002/anie.200453849.
Zotero 插件