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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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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. |
format | Online Article Text |
id | pubmed-6692172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
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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