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

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 quaterna...

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Autores principales: Weißgraeber, Stephanie, Saponaro, Andrea, Thiel, Gerhard, Hamacher, Kay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225470/
https://www.ncbi.nlm.nih.gov/pubmed/28074902
http://dx.doi.org/10.1038/srep40168
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author Weißgraeber, Stephanie
Saponaro, Andrea
Thiel, Gerhard
Hamacher, Kay
author_facet Weißgraeber, Stephanie
Saponaro, Andrea
Thiel, Gerhard
Hamacher, Kay
author_sort Weißgraeber, Stephanie
collection PubMed
description 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.
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spelling pubmed-52254702017-01-17 A reduced mechanical model for cAMP-modulated gating in HCN channels Weißgraeber, Stephanie Saponaro, Andrea Thiel, Gerhard Hamacher, Kay Sci Rep Article 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. Nature Publishing Group 2017-01-11 /pmc/articles/PMC5225470/ /pubmed/28074902 http://dx.doi.org/10.1038/srep40168 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Weißgraeber, Stephanie
Saponaro, Andrea
Thiel, Gerhard
Hamacher, Kay
A reduced mechanical model for cAMP-modulated gating in HCN channels
title A reduced mechanical model for cAMP-modulated gating in HCN channels
title_full A reduced mechanical model for cAMP-modulated gating in HCN channels
title_fullStr A reduced mechanical model for cAMP-modulated gating in HCN channels
title_full_unstemmed A reduced mechanical model for cAMP-modulated gating in HCN channels
title_short A reduced mechanical model for cAMP-modulated gating in HCN channels
title_sort reduced mechanical model for camp-modulated gating in hcn channels
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5225470/
https://www.ncbi.nlm.nih.gov/pubmed/28074902
http://dx.doi.org/10.1038/srep40168
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