Individual Ion Binding Sites in the K+ Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation

Matulef, Kimberly; Annen, Alvin W.; Nix, Jay C.; Valiyaveetil, Francis I.

doi:10.1016/j.str.2016.02.021

Title: Individual Ion Binding Sites in the K+ Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation

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Abstract

The selectivity filter of K⁺ channels contains four ion binding sites (S1–S4) and serves dual functions of discriminating K⁺ from Na⁺ and acting as a gate during C-type inactivation. C-type inactivation is modulated by ion binding to the selectivity filter sites, but the underlying mechanism is not known. We evaluate how the ion binding sites in the selectivity filter of the KcsA channel participate in C-type inactivation and in recovery from inactivation. We use unnatural amide-to-ester substitutions in the protein backbone to manipulate the S1–S3 sites and a side-chain substitution to perturb the S4 site. We then develop an improved semisynthetic approach for generating these amide-to-ester substitutions in the selectivity filter. This combined electrophysiological and X-ray crystallographic analysis of the selectivity filter mutants show that the ion binding sites play specific roles during inactivation and provide insights into the structural changes at the selectivity filter during C-type inactivation.

Authors:: Matulef, Kimberly; Annen, Alvin W.; Nix, Jay C.; Valiyaveetil, Francis I.

Publication Date:: Sun May 01 00:00:00 EDT 2016

Research Org.:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)

OSTI Identifier:: 1355063

Alternate Identifier(s):: OSTI ID: 1414756

Grant/Contract Number:: AC03-76SF00098; AC02-05CH11231; GM087546

Resource Type:: Published Article

Journal Name:: Structure

Additional Journal Information:: Journal Name: Structure Journal Volume: 24 Journal Issue: 5; Journal ID: ISSN 0969-2126

Publisher:: Elsevier

Country of Publication:: United Kingdom

Language:: English

Subject:: 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES

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                    Matulef, Kimberly, Annen, Alvin W., Nix, Jay C., and Valiyaveetil, Francis I. Individual Ion Binding Sites in the K+ Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation.  United Kingdom: N. p., 2016. 
Web.  doi:10.1016/j.str.2016.02.021.

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                    Matulef, Kimberly, Annen, Alvin W., Nix, Jay C., & Valiyaveetil, Francis I. Individual Ion Binding Sites in the K+ Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation.  United Kingdom.  https://doi.org/10.1016/j.str.2016.02.021

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                    Matulef, Kimberly, Annen, Alvin W., Nix, Jay C., and Valiyaveetil, Francis I. Sun .  
"Individual Ion Binding Sites in the K+ Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation".  United Kingdom.  https://doi.org/10.1016/j.str.2016.02.021.

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@article{osti_1355063,

  title        = {Individual Ion Binding Sites in the K+ Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation},

  author       = {Matulef, Kimberly and Annen, Alvin W. and Nix, Jay C. and Valiyaveetil, Francis I.},

  abstractNote = {The selectivity filter of K+ channels contains four ion binding sites (S1–S4) and serves dual functions of discriminating K+ from Na+ and acting as a gate during C-type inactivation. C-type inactivation is modulated by ion binding to the selectivity filter sites, but the underlying mechanism is not known. We evaluate how the ion binding sites in the selectivity filter of the KcsA channel participate in C-type inactivation and in recovery from inactivation. We use unnatural amide-to-ester substitutions in the protein backbone to manipulate the S1–S3 sites and a side-chain substitution to perturb the S4 site. We then develop an improved semisynthetic approach for generating these amide-to-ester substitutions in the selectivity filter. This combined electrophysiological and X-ray crystallographic analysis of the selectivity filter mutants show that the ion binding sites play specific roles during inactivation and provide insights into the structural changes at the selectivity filter during C-type inactivation.},

  doi          = {10.1016/j.str.2016.02.021},

  journal      = {Structure},

  number       = 5,

  volume       = 24,

  place        = {United Kingdom},

  year         = {Sun May 01 00:00:00 EDT 2016},

  month        = {Sun May 01 00:00:00 EDT 2016}

}

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