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Two separate interfaces between the Voltage sensor and pore are required for the function of Voltage-dependent K+ channels

Publication ,  Journal Article
Lee, SY; Banerjee, A; Mackinnon, R
Published in: PLoS Biology
March 1, 2009

Voltage-dependent K+(Kv) channels gate open in response to the membrane voltage. To further our understanding of how cell membrane voltage regulates the opening of a Kv channel, we have studied the protein interfaces that attach the voltage-sensor domains to the pore. In the crystal structure, three physical interfaces exist. Only two of these consist of amino acids that are co-evolved across the interface between voltage sensor and pore according to statistical coupling analysis of 360 Kv channel sequences. A first co-evolved interface is formed by the S4-S5 linkers (one from each of four voltage sensors), which form a cuff surrounding the S6-lined pore opening at the intracellular surface. The crystal structure and published mutational studies support the hypothesis that the S4-S5 linkers convert voltagesensor motions directly into gate opening and closing. A second co-evolved interface forms a small contact surface between S1 of the voltage sensor and the pore helix near the extracellular surface. We demonstrate through mutagenesis that this interface is necessary for the function and/or structure of two different Kv channels. This second interface is well positioned to act as a second anchor point between the voltage sensor and the pore, thus allowing efficient transmission of conformational changes to the pore's gate. Copyright: © 2009 Lee et al. This is an open-access article distributed under the.

Duke Scholars

Published In

PLoS Biology

DOI

EISSN

1545-7885

ISSN

1544-9173

Publication Date

March 1, 2009

Volume

7

Issue

3

Start / End Page

0676 / 0686

Related Subject Headings

  • Developmental Biology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 30 Agricultural, veterinary and food sciences
  • 11 Medical and Health Sciences
  • 07 Agricultural and Veterinary Sciences
  • 06 Biological Sciences
 

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Lee, S. Y., Banerjee, A., & Mackinnon, R. (2009). Two separate interfaces between the Voltage sensor and pore are required for the function of Voltage-dependent K+ channels. PLoS Biology, 7(3), 0676–0686. https://doi.org/10.1371/journal.pbio.1000047-S.pdf
Lee, S. Y., A. Banerjee, and R. Mackinnon. “Two separate interfaces between the Voltage sensor and pore are required for the function of Voltage-dependent K+ channels.” PLoS Biology 7, no. 3 (March 1, 2009): 0676–86. https://doi.org/10.1371/journal.pbio.1000047-S.pdf.
Lee, S. Y., et al. “Two separate interfaces between the Voltage sensor and pore are required for the function of Voltage-dependent K+ channels.” PLoS Biology, vol. 7, no. 3, Mar. 2009, pp. 0676–86. Scopus, doi:10.1371/journal.pbio.1000047-S.pdf.
Journal cover image

Published In

PLoS Biology

DOI

EISSN

1545-7885

ISSN

1544-9173

Publication Date

March 1, 2009

Volume

7

Issue

3

Start / End Page

0676 / 0686

Related Subject Headings

  • Developmental Biology
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 30 Agricultural, veterinary and food sciences
  • 11 Medical and Health Sciences
  • 07 Agricultural and Veterinary Sciences
  • 06 Biological Sciences