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The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization

Voltage-gated ion channels (VGICs) contain positively-charged residues within the S4 helix of the voltage-sensing domain (VSD) that are displaced in response to changes in transmembrane voltage, promoting conformational changes that open the pore. Pacemaker HCN channels are unique among VGICs becaus...

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Detalles Bibliográficos
Autores principales: Dai, Gucan, Aman, Teresa K., DiMaio, Frank, Zagotta, William N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692172/
https://www.ncbi.nlm.nih.gov/pubmed/31285608
http://dx.doi.org/10.1038/s41594-019-0259-1
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author Dai, Gucan
Aman, Teresa K.
DiMaio, Frank
Zagotta, William N.
author_facet Dai, Gucan
Aman, Teresa K.
DiMaio, Frank
Zagotta, William N.
author_sort Dai, Gucan
collection PubMed
description Voltage-gated ion channels (VGICs) contain positively-charged residues within the S4 helix of the voltage-sensing domain (VSD) that are displaced in response to changes in transmembrane voltage, promoting conformational changes that open the pore. Pacemaker HCN channels are unique among VGICs because their open probability is increased by membrane hyperpolarization rather than depolarization. Here we measured the precise movement of the S4 helix of a sea urchin HCN channel using transition metal ion fluorescence resonance energy transfer (tmFRET). We show that the S4 undergoes a significant (~10 Å) downward movement in response to membrane hyperpolarization. Furthermore, by applying distance constraints determined from tmFRET experiments to Rosetta modeling, we reveal that the C-terminal part of the S4 helix exhibits an unexpected tilting motion during hyperpolarization activation. These data provide a long-sought glimpse of the hyperpolarized state of a functioning VSD and also a framework for understanding the dynamics of reverse gating in HCN channels.
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spelling pubmed-66921722020-01-08 The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization Dai, Gucan Aman, Teresa K. DiMaio, Frank Zagotta, William N. Nat Struct Mol Biol Article Voltage-gated ion channels (VGICs) contain positively-charged residues within the S4 helix of the voltage-sensing domain (VSD) that are displaced in response to changes in transmembrane voltage, promoting conformational changes that open the pore. Pacemaker HCN channels are unique among VGICs because their open probability is increased by membrane hyperpolarization rather than depolarization. Here we measured the precise movement of the S4 helix of a sea urchin HCN channel using transition metal ion fluorescence resonance energy transfer (tmFRET). We show that the S4 undergoes a significant (~10 Å) downward movement in response to membrane hyperpolarization. Furthermore, by applying distance constraints determined from tmFRET experiments to Rosetta modeling, we reveal that the C-terminal part of the S4 helix exhibits an unexpected tilting motion during hyperpolarization activation. These data provide a long-sought glimpse of the hyperpolarized state of a functioning VSD and also a framework for understanding the dynamics of reverse gating in HCN channels. 2019-07-08 2019-08 /pmc/articles/PMC6692172/ /pubmed/31285608 http://dx.doi.org/10.1038/s41594-019-0259-1 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Dai, Gucan
Aman, Teresa K.
DiMaio, Frank
Zagotta, William N.
The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
title The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
title_full The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
title_fullStr The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
title_full_unstemmed The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
title_short The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
title_sort hcn channel voltage sensor undergoes a large downward motion during hyperpolarization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692172/
https://www.ncbi.nlm.nih.gov/pubmed/31285608
http://dx.doi.org/10.1038/s41594-019-0259-1
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