Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.

KCa3.1 (also known as SK4 or IK1) is a mammalian intermediate-conductance potassium channel that plays a critical role in the activation of T cells, B cells, and mast cells, effluxing potassium ions to maintain a negative membrane potential for influxing calcium ions. KCa3.1 shares primary sequence...

Full description

Saved in:
Bibliographic Details
Main Authors: Tianyang Ji, Senena Corbalán-García, Stevan R Hubbard
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199942&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849766308488413184
author Tianyang Ji
Senena Corbalán-García
Stevan R Hubbard
author_facet Tianyang Ji
Senena Corbalán-García
Stevan R Hubbard
author_sort Tianyang Ji
collection DOAJ
description KCa3.1 (also known as SK4 or IK1) is a mammalian intermediate-conductance potassium channel that plays a critical role in the activation of T cells, B cells, and mast cells, effluxing potassium ions to maintain a negative membrane potential for influxing calcium ions. KCa3.1 shares primary sequence similarity with three other (low-conductance) potassium channels: KCa2.1, KCa2.2, and KCa2.3 (also known as SK1-3). These four homotetrameric channels bind calmodulin (CaM) in the cytoplasmic region, and calcium binding to CaM triggers channel activation. Unique to KCa3.1, activation also requires phosphorylation of a single histidine residue, His358, in the cytoplasmic region, which relieves copper-mediated inhibition of the channel. Near the cytoplasmic C-terminus of KCa3.1 (and KCa2.1-2.3), secondary-structure analysis predicts the presence of a coiled-coil/heptad repeat. Here, we report the crystal structure of the C-terminal coiled-coil region of KCa3.1, which forms a parallel four-helix bundle, consistent with the tetrameric nature of the channel. Interestingly, the four copies of a histidine residue, His389, in an 'a' position within the heptad repeat, are observed to bind a copper ion along the four-fold axis of the bundle. These results suggest that His358, the inhibitory histidine in KCa3.1, might coordinate a copper ion through a similar binding mode.
format Article
id doaj-art-08c2e39af35a4064a99714b33c6defc2
institution DOAJ
issn 1932-6203
language English
publishDate 2018-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-08c2e39af35a4064a99714b33c6defc22025-08-20T03:04:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01136e019994210.1371/journal.pone.0199942Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.Tianyang JiSenena Corbalán-GarcíaStevan R HubbardKCa3.1 (also known as SK4 or IK1) is a mammalian intermediate-conductance potassium channel that plays a critical role in the activation of T cells, B cells, and mast cells, effluxing potassium ions to maintain a negative membrane potential for influxing calcium ions. KCa3.1 shares primary sequence similarity with three other (low-conductance) potassium channels: KCa2.1, KCa2.2, and KCa2.3 (also known as SK1-3). These four homotetrameric channels bind calmodulin (CaM) in the cytoplasmic region, and calcium binding to CaM triggers channel activation. Unique to KCa3.1, activation also requires phosphorylation of a single histidine residue, His358, in the cytoplasmic region, which relieves copper-mediated inhibition of the channel. Near the cytoplasmic C-terminus of KCa3.1 (and KCa2.1-2.3), secondary-structure analysis predicts the presence of a coiled-coil/heptad repeat. Here, we report the crystal structure of the C-terminal coiled-coil region of KCa3.1, which forms a parallel four-helix bundle, consistent with the tetrameric nature of the channel. Interestingly, the four copies of a histidine residue, His389, in an 'a' position within the heptad repeat, are observed to bind a copper ion along the four-fold axis of the bundle. These results suggest that His358, the inhibitory histidine in KCa3.1, might coordinate a copper ion through a similar binding mode.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199942&type=printable
spellingShingle Tianyang Ji
Senena Corbalán-García
Stevan R Hubbard
Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.
PLoS ONE
title Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.
title_full Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.
title_fullStr Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.
title_full_unstemmed Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.
title_short Crystal structure of the C-terminal four-helix bundle of the potassium channel KCa3.1.
title_sort crystal structure of the c terminal four helix bundle of the potassium channel kca3 1
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0199942&type=printable
work_keys_str_mv AT tianyangji crystalstructureofthecterminalfourhelixbundleofthepotassiumchannelkca31
AT senenacorbalangarcia crystalstructureofthecterminalfourhelixbundleofthepotassiumchannelkca31
AT stevanrhubbard crystalstructureofthecterminalfourhelixbundleofthepotassiumchannelkca31