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cAMP 调节 HCN 通道门控的简化力学模型。

A reduced mechanical model for cAMP-modulated gating in HCN channels.

机构信息

Department of Biology, TU Darmstadt, Germany.

Dept. of Biosciences, University of Milan, 20133 Milan, Italy.

出版信息

Sci Rep. 2017 Jan 11;7:40168. doi: 10.1038/srep40168.

DOI:10.1038/srep40168
PMID:28074902
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5225470/
Abstract

We developed an in silico mechanical model to analyze the process of cAMP-induced conformational modulations in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which conduct cations across the membrane of mammalian heart and brain cells. The structural analysis reveals a quaternary twist in the cytosolic parts of the four subunits in the channel tetramer. This motion augments the intrinsic dynamics of the very same protein structure. The pronounced differences between the cAMP bound and unbound form include a mutual interaction between the C-linker of the cyclic nucleotide binding domain (CNBD) and the linker between the S4 and S5 transmembrane domain of the channel. This allows a mechanistic annotation of the twisting motion in relation to the allosteric modulation of voltage-dependent gating of this channel by cAMP.

摘要

我们开发了一个计算力学模型来分析 cAMP 诱导的 hyperpolarization-activated cyclic nucleotide-gated (HCN) 通道构象调制的过程，该通道在哺乳动物心脏和脑细胞的膜上传导阳离子。结构分析揭示了通道四聚体中四个亚基胞质部分的四级扭转。这种运动增强了蛋白质结构的固有动力学。与 cAMP 结合和未结合形式之间的显著差异包括环核苷酸结合域 (CNBD) 的 C 接头与通道 S4 和 S5 跨膜域之间的接头之间的相互作用。这允许对扭转运动进行机制注释，与 cAMP 对该通道电压依赖性门控的变构调节有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/59e0c089b82a/srep40168-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/998d2192afb0/srep40168-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/62b9d65749fd/srep40168-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/04fa668d8d74/srep40168-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/fa6e00f26b8e/srep40168-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/639ede8d7430/srep40168-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/59e0c089b82a/srep40168-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/998d2192afb0/srep40168-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/62b9d65749fd/srep40168-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/04fa668d8d74/srep40168-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/fa6e00f26b8e/srep40168-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/639ede8d7430/srep40168-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a500/5225470/59e0c089b82a/srep40168-f6.jpg

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本文引用的文献

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Biophys J. 2015 Dec 1;109(11):2268-76. doi: 10.1016/j.bpj.2015.08.054.
2
Computing the Amino Acid Specificity of Fluctuations in Biomolecular Systems.计算生物分子系统中波动的氨基酸特异性
J Chem Theory Comput. 2006 May;2(3):873-8. doi: 10.1021/ct050247s.
3
Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.环磷酸腺苷（cAMP）与TRIP8b在调节超极化激活的环核苷酸门控（HCN）通道功能中相互拮抗作用的结构基础
LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.
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Elife. 2024 Apr 23;12:RP92411. doi: 10.7554/eLife.92411.
4
LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.LRMP通过破坏分子内信号转导来抑制HCN4通道的cAMP增强作用。
bioRxiv. 2024 Jan 24:2023.08.29.555242. doi: 10.1101/2023.08.29.555242.
5
Uncoupling of Voltage- and Ligand-Induced Activation in HCN2 Channels by Glycine Inserts.甘氨酸插入导致HCN2通道中电压和配体诱导激活的解偶联
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6
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7
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4
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10
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