Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+) channels.

Published

Journal Article

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 voltage-sensor 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.

Full Text

Duke Authors

Cited Authors

  • Lee, S-Y; Banerjee, A; MacKinnon, R

Published Date

  • March 3, 2009

Published In

Volume / Issue

  • 7 / 3

Start / End Page

  • e47 -

PubMed ID

  • 19260762

Pubmed Central ID

  • 19260762

Electronic International Standard Serial Number (EISSN)

  • 1545-7885

Digital Object Identifier (DOI)

  • 10.1371/journal.pbio.1000047

Language

  • eng

Conference Location

  • United States