Cargando…
A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel
Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluorina...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644096/ https://www.ncbi.nlm.nih.gov/pubmed/23653196 http://dx.doi.org/10.1038/ncomms2761 |
_version_ | 1782268421034999808 |
---|---|
author | Pless, Stephan A. Niciforovic, Ana P. Galpin, Jason D. Nunez, John-Jose Kurata, Harley T. Ahern, Christopher A. |
author_facet | Pless, Stephan A. Niciforovic, Ana P. Galpin, Jason D. Nunez, John-Jose Kurata, Harley T. Ahern, Christopher A. |
author_sort | Pless, Stephan A. |
collection | PubMed |
description | Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluorinated derivatives of aromatic residues previously implicated in the gating of Shaker potassium channels. Here we show that stepwise dispersion of the negative electrostatic surface potential of only one site, Phe481, stabilizes the channel open state. Furthermore, these data suggest that this apparent stabilization is the consequence of the amelioration of an inherently repulsive open-state interaction between the partial negative charge on the face of Phe481 and a highly co-evolved acidic side chain, Glu395, and this interaction is potentially modulated through the Tyr485 hydroxyl. We propose that the intrinsic open-state destabilization via aromatic repulsion represents a new mechanism by which ion channels, and likely other proteins, fine-tune conformational equilibria. |
format | Online Article Text |
id | pubmed-3644096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-36440962013-05-17 A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel Pless, Stephan A. Niciforovic, Ana P. Galpin, Jason D. Nunez, John-Jose Kurata, Harley T. Ahern, Christopher A. Nat Commun Article Voltage-gated potassium channels elicit membrane hyperpolarization through voltage-sensor domains that regulate the conductive status of the pore domain. To better understand the inherent basis for the open-closed equilibrium in these channels, we undertook an atomistic scan using synthetic fluorinated derivatives of aromatic residues previously implicated in the gating of Shaker potassium channels. Here we show that stepwise dispersion of the negative electrostatic surface potential of only one site, Phe481, stabilizes the channel open state. Furthermore, these data suggest that this apparent stabilization is the consequence of the amelioration of an inherently repulsive open-state interaction between the partial negative charge on the face of Phe481 and a highly co-evolved acidic side chain, Glu395, and this interaction is potentially modulated through the Tyr485 hydroxyl. We propose that the intrinsic open-state destabilization via aromatic repulsion represents a new mechanism by which ion channels, and likely other proteins, fine-tune conformational equilibria. Nature Pub. Group 2013-04-30 /pmc/articles/PMC3644096/ /pubmed/23653196 http://dx.doi.org/10.1038/ncomms2761 Text en Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Pless, Stephan A. Niciforovic, Ana P. Galpin, Jason D. Nunez, John-Jose Kurata, Harley T. Ahern, Christopher A. A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel |
title | A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel |
title_full | A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel |
title_fullStr | A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel |
title_full_unstemmed | A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel |
title_short | A novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel |
title_sort | novel mechanism for fine-tuning open-state stability in a voltage-gated potassium channel |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644096/ https://www.ncbi.nlm.nih.gov/pubmed/23653196 http://dx.doi.org/10.1038/ncomms2761 |
work_keys_str_mv | AT plessstephana anovelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT niciforovicanap anovelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT galpinjasond anovelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT nunezjohnjose anovelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT kurataharleyt anovelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT ahernchristophera anovelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT plessstephana novelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT niciforovicanap novelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT galpinjasond novelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT nunezjohnjose novelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT kurataharleyt novelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel AT ahernchristophera novelmechanismforfinetuningopenstatestabilityinavoltagegatedpotassiumchannel |