The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel

Daniel L. Minor; Yu Fung Lin; Bret C. Mobley; Abigail Avelar; Yuh Nung Jan; Lily Y. Jan; James M. Berger

doi:10.1016/S0092-8674(00)00088-X

The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel

Daniel L. Minor, Yu Fung Lin, Bret C. Mobley, Abigail Avelar, Yuh Nung Jan, Lily Y. Jan, James M. Berger

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153 Scopus citations

Abstract

Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the closed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.

Original language	English (US)
Pages (from-to)	657-670
Number of pages	14
Journal	Cell
Volume	102
Issue number	5
DOIs	https://doi.org/10.1016/S0092-8674(00)00088-X
State	Published - Sep 1 2000
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/S0092-8674(00)00088-X

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title = "The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel",

abstract = "Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the closed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.",

author = "Minor, {Daniel L.} and Lin, {Yu Fung} and Mobley, {Bret C.} and Abigail Avelar and Jan, {Yuh Nung} and Jan, {Lily Y.} and Berger, {James M.}",

note = "Funding Information: We thank T. Earnest and staff at ALS beamline 5.0.2 for help with data collection; S. Jaswal and D. A. Agard for use of the CD; M. Yu for molecular biology assistance; and members of the Jan lab for helpful discussions. D. L. M. thanks R. Aldrich, D. Barrick, E. Isacoff, and N. Unwin for insightful discussions. Y. N. Jan and L. Y. Jan are HHMI investigators. This work was supported by an NIH grant.",

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doi = "10.1016/S0092-8674(00)00088-X",

language = "English (US)",

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T1 - The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel

AU - Minor, Daniel L.

AU - Lin, Yu Fung

AU - Mobley, Bret C.

AU - Avelar, Abigail

AU - Jan, Yuh Nung

AU - Jan, Lily Y.

AU - Berger, James M.

N1 - Funding Information: We thank T. Earnest and staff at ALS beamline 5.0.2 for help with data collection; S. Jaswal and D. A. Agard for use of the CD; M. Yu for molecular biology assistance; and members of the Jan lab for helpful discussions. D. L. M. thanks R. Aldrich, D. Barrick, E. Isacoff, and N. Unwin for insightful discussions. Y. N. Jan and L. Y. Jan are HHMI investigators. This work was supported by an NIH grant.

PY - 2000/9/1

Y1 - 2000/9/1

N2 - Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the closed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.

AB - Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the closed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.

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VL - 102

SP - 657

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JO - Cell

JF - Cell

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The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel

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