Cargando…
The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition
Pannexins are large-pore forming channels responsible for ATP release under a variety of physiological and pathological conditions. Although predicted to share similar membrane topology with other large-pore forming proteins such as connexins, innexins, and LRRC8, pannexins have minimal sequence sim...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108861/ https://www.ncbi.nlm.nih.gov/pubmed/32048993 http://dx.doi.org/10.7554/eLife.54670 |
_version_ | 1783512851646775296 |
---|---|
author | Michalski, Kevin Syrjanen, Johanna L Henze, Erik Kumpf, Julia Furukawa, Hiro Kawate, Toshimitsu |
author_facet | Michalski, Kevin Syrjanen, Johanna L Henze, Erik Kumpf, Julia Furukawa, Hiro Kawate, Toshimitsu |
author_sort | Michalski, Kevin |
collection | PubMed |
description | Pannexins are large-pore forming channels responsible for ATP release under a variety of physiological and pathological conditions. Although predicted to share similar membrane topology with other large-pore forming proteins such as connexins, innexins, and LRRC8, pannexins have minimal sequence similarity to these protein families. Here, we present the cryo-EM structure of a frog pannexin 1 (Panx1) channel at 3.0 Å. We find that Panx1 protomers harbor four transmembrane helices similar in arrangement to other large-pore forming proteins but assemble as a heptameric channel with a unique constriction formed by Trp74 in the first extracellular loop. Mutating Trp74 or the nearby Arg75 disrupt ion selectivity, whereas altering residues in the hydrophobic groove formed by the two extracellular loops abrogates channel inhibition by carbenoxolone. Our structural and functional study establishes the extracellular loops as important structural motifs for ion selectivity and channel inhibition in Panx1. |
format | Online Article Text |
id | pubmed-7108861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-71088612020-04-01 The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition Michalski, Kevin Syrjanen, Johanna L Henze, Erik Kumpf, Julia Furukawa, Hiro Kawate, Toshimitsu eLife Neuroscience Pannexins are large-pore forming channels responsible for ATP release under a variety of physiological and pathological conditions. Although predicted to share similar membrane topology with other large-pore forming proteins such as connexins, innexins, and LRRC8, pannexins have minimal sequence similarity to these protein families. Here, we present the cryo-EM structure of a frog pannexin 1 (Panx1) channel at 3.0 Å. We find that Panx1 protomers harbor four transmembrane helices similar in arrangement to other large-pore forming proteins but assemble as a heptameric channel with a unique constriction formed by Trp74 in the first extracellular loop. Mutating Trp74 or the nearby Arg75 disrupt ion selectivity, whereas altering residues in the hydrophobic groove formed by the two extracellular loops abrogates channel inhibition by carbenoxolone. Our structural and functional study establishes the extracellular loops as important structural motifs for ion selectivity and channel inhibition in Panx1. eLife Sciences Publications, Ltd 2020-02-12 /pmc/articles/PMC7108861/ /pubmed/32048993 http://dx.doi.org/10.7554/eLife.54670 Text en © 2020, Michalski et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Michalski, Kevin Syrjanen, Johanna L Henze, Erik Kumpf, Julia Furukawa, Hiro Kawate, Toshimitsu The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition |
title | The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition |
title_full | The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition |
title_fullStr | The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition |
title_full_unstemmed | The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition |
title_short | The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition |
title_sort | cryo-em structure of pannexin 1 reveals unique motifs for ion selection and inhibition |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108861/ https://www.ncbi.nlm.nih.gov/pubmed/32048993 http://dx.doi.org/10.7554/eLife.54670 |
work_keys_str_mv | AT michalskikevin thecryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT syrjanenjohannal thecryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT henzeerik thecryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT kumpfjulia thecryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT furukawahiro thecryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT kawatetoshimitsu thecryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT michalskikevin cryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT syrjanenjohannal cryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT henzeerik cryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT kumpfjulia cryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT furukawahiro cryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition AT kawatetoshimitsu cryoemstructureofpannexin1revealsuniquemotifsforionselectionandinhibition |