• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

通过单分子测量验证HCN通道与其神经元调节因子TRIP8b之间的结合化学计量。

Validation of the binding stoichiometry between HCN channels and their neuronal regulator TRIP8b by single molecule measurements.

作者信息

Saponaro Andrea, Vallese Francesca, Porro Alessandro, Clarke Oliver B

机构信息

Department of Biosciences, University of Milan, Milano, Italy.

Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, United States.

出版信息

Front Physiol. 2022 Sep 26;13:998176. doi: 10.3389/fphys.2022.998176. eCollection 2022.

DOI:10.3389/fphys.2022.998176
PMID:36225302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9549148/
Abstract

Tetratricopeptide repeat-containing Rab8b-interacting (TRIP8b) protein is a brain-specific subunit of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels, a class of voltage-gated channels modulated by cyclic nucleotides. While the interaction between TRIP8b and the cytosolic C terminus of the channel has been structurally described, the HCN:TRIP8b stoichiometry is less characterized. We employed single molecule mass photometry (MP) to image HCN4 particles purified in complex with TRIP8b. Our data show that four TRIP8b subunits are bound to the tetrameric HCN4 particle, confirming a 1:1 stoichiometry.

摘要

含四肽重复序列的Rab8b相互作用蛋白（TRIP8b）是超极化激活的环核苷酸门控（HCN）通道的脑特异性亚基，HCN通道是一类受环核苷酸调节的电压门控通道。虽然TRIP8b与通道胞质C末端之间的相互作用已在结构上有所描述，但HCN:TRIP8b的化学计量关系却鲜为人知。我们采用单分子质量光度法（MP）对与TRIP8b复合纯化的HCN4颗粒进行成像。我们的数据表明，四个TRIP8b亚基与四聚体HCN4颗粒结合，证实了1:1的化学计量关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e3/9549148/397b290939e9/fphys-13-998176-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e3/9549148/520597cbde50/fphys-13-998176-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e3/9549148/397b290939e9/fphys-13-998176-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e3/9549148/520597cbde50/fphys-13-998176-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76e3/9549148/397b290939e9/fphys-13-998176-g002.jpg

相似文献

1
Validation of the binding stoichiometry between HCN channels and their neuronal regulator TRIP8b by single molecule measurements.通过单分子测量验证HCN通道与其神经元调节因子TRIP8b之间的结合化学计量。
Front Physiol. 2022 Sep 26;13:998176. doi: 10.3389/fphys.2022.998176. eCollection 2022.
2
Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites.超极化激活环核苷酸门控通道的运输和门控由与四肽重复结构域包含 Rab8b 相互作用蛋白（TRIP8b）和环 AMP 在不同位点的相互作用调节。
J Biol Chem. 2011 Jun 10;286(23):20823-34. doi: 10.1074/jbc.M111.236125. Epub 2011 Apr 19.
3
Deletion of the hyperpolarization-activated cyclic nucleotide-gated channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice.缺失超极化激活环核苷酸门控通道辅助亚基 TRIP8b 会损害海马 Ih 的定位和功能，并促进小鼠的抗抑郁行为。
J Neurosci. 2011 May 18;31(20):7424-40. doi: 10.1523/JNEUROSCI.0936-11.2011.
4
Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels.三聚体 G 蛋白偶联受体相互作用蛋白 8b 亚基与超极化激活环核苷酸门控通道相互作用的结构和化学计量。
Proc Natl Acad Sci U S A. 2012 May 15;109(20):7899-904. doi: 10.1073/pnas.1201997109. Epub 2012 May 1.
5
Rational design of a mutation to investigate the role of the brain protein TRIP8b in limiting the cAMP response of HCN channels in neurons.理性设计一种突变，以研究脑蛋白 TRIP8b 在限制神经元中 HCN 通道的 cAMP 反应中的作用。
J Gen Physiol. 2020 Sep 7;152(9). doi: 10.1085/jgp.202012596.
6
Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b.鉴定HCN1与TRIP8b之间蛋白质-蛋白质相互作用的小分子抑制剂的方法
J Vis Exp. 2016 Nov 11(117):54540. doi: 10.3791/54540.
7
The structure and function of TRIP8b, an auxiliary subunit of hyperpolarization-activated cyclic-nucleotide gated channels.TRIP8b 的结构与功能，超极化激活环核苷酸门控通道的辅助亚基。
Channels (Austin). 2020 Dec;14(1):110-122. doi: 10.1080/19336950.2020.1740501.
8
Discovery of a small-molecule inhibitor of the TRIP8b-HCN interaction with efficacy in neurons.发现一种小分子抑制剂，可阻断 TRIP8b-HCN 相互作用，在神经元中具有疗效。
J Biol Chem. 2022 Jul;298(7):102069. doi: 10.1016/j.jbc.2022.102069. Epub 2022 May 24.
9
HCN-channel dendritic targeting requires bipartite interaction with TRIP8b and regulates antidepressant-like behavioral effects.HCN通道的树突靶向需要与TRIP8b进行二元相互作用，并调节抗抑郁样行为效应。
Mol Psychiatry. 2017 Mar;22(3):458-465. doi: 10.1038/mp.2016.99. Epub 2016 Jul 12.
10
Allostery between two binding sites in the ion channel subunit TRIP8b confers binding specificity to HCN channels.离子通道亚基TRIP8b中两个结合位点之间的变构作用赋予了超极化激活的环核苷酸门控通道（HCN通道）结合特异性。
J Biol Chem. 2017 Oct 27;292(43):17718-17730. doi: 10.1074/jbc.M117.802256. Epub 2017 Sep 8.

本文引用的文献

1
Gating movements and ion permeation in HCN4 pacemaker channels.HCN4 起搏通道中的门控运动和离子渗透。
Mol Cell. 2021 Jul 15;81(14):2929-2943.e6. doi: 10.1016/j.molcel.2021.05.033. Epub 2021 Jun 23.
2
Detection of ligand binding to purified HCN channels using fluorescence-based size exclusion chromatography.使用基于荧光的排阻色谱法检测配体与纯化 HCN 通道的结合。
Methods Enzymol. 2021;652:105-123. doi: 10.1016/bs.mie.2021.01.043. Epub 2021 Feb 27.
3
Rational design of a mutation to investigate the role of the brain protein TRIP8b in limiting the cAMP response of HCN channels in neurons.
理性设计一种突变，以研究脑蛋白 TRIP8b 在限制神经元中 HCN 通道的 cAMP 反应中的作用。
J Gen Physiol. 2020 Sep 7;152(9). doi: 10.1085/jgp.202012596.
4
The HCN domain couples voltage gating and cAMP response in hyperpolarization-activated cyclic nucleotide-gated channels.HCN 结构域将电压门控和 cAMP 反应偶联在超极化激活环核苷酸门控通道中。
Elife. 2019 Nov 26;8:e49672. doi: 10.7554/eLife.49672.
5
Mechanical transduction of cytoplasmic-to-transmembrane-domain movements in a hyperpolarization-activated cyclic nucleotide-gated cation channel.机械转导超极化激活环核苷酸门控阳离子通道细胞质到跨膜结构域的运动。
J Biol Chem. 2018 Aug 17;293(33):12908-12918. doi: 10.1074/jbc.RA118.002139. Epub 2018 Jun 23.
6
A synthetic peptide that prevents cAMP regulation in mammalian hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.一种能阻止哺乳类超极化激活环核苷酸门控 (HCN) 通道中 cAMP 调节的合成肽。
Elife. 2018 Jun 20;7:e35753. doi: 10.7554/eLife.35753.
7
Quantitative mass imaging of single biological macromolecules.单生物大分子的定量质量成像。
Science. 2018 Apr 27;360(6387):423-427. doi: 10.1126/science.aar5839.
8
Mechanism for the inhibition of the cAMP dependence of HCN ion channels by the auxiliary subunit TRIP8b.辅助亚基TRIP8b抑制HCN离子通道对cAMP依赖性的机制。
J Biol Chem. 2017 Oct 27;292(43):17794-17803. doi: 10.1074/jbc.M117.800722. Epub 2017 Sep 1.
9
Structures of the Human HCN1 Hyperpolarization-Activated Channel.人类超极化激活的环核苷酸门控通道1（HCN1）的结构
Cell. 2017 Jan 12;168(1-2):111-120.e11. doi: 10.1016/j.cell.2016.12.023.
10
Functional Analysis of Orai1 Concatemers Supports a Hexameric Stoichiometry for the CRAC Channel.Orai1串联体的功能分析支持CRAC通道的六聚体化学计量。
Biophys J. 2016 Nov 1;111(9):1897-1907. doi: 10.1016/j.bpj.2016.09.020.