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

2018· article· en· 12 citations· W2810530720 on OpenAlex· 10.1371/journal.pone.0199942

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Canadian funderA Canadian agency funded it. The work may carry no Canadian affiliation at all.

No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.

The three-model screen

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All three models called this out of scope.

stratum: fund_new · design weight: 1678.90 (the sample is stratified; any rate computed without the weight is wrong)
Claude Opus 4.8OUT
genre: empirical
about Canada: no
confidence: high

Crystal structure of a potassium channel domain; structural biology.

GPT-5.6 (high)OUT
genre: empirical
about Canada: no
confidence: high

The study reports a crystal structure and biological implications of a potassium channel.

Grok 4.5OUT
genre: empirical
about Canada: no
confidence: high

Crystal structure of a potassium channel domain is structural biology domain research.

Abstract

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.

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The record

Venue
PLoS ONE
Topic
Ion channel regulation and function
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
National Institute of Allergy and Infectious DiseasesNational Institute of General Medical SciencesSchool of Medicine, New York UniversityYork University
Keywords
Potassium channelChemistryCalcium-activated potassium channelHistidineIon channelBiophysicsBK channelHelix bundleCrystallographyCalmodulinProtein structureBiochemistryBiologyAmino acidReceptor
Has abstract in OpenAlex
yes