Two separate interfaces between the voltage sensor and pore are required for the function of voltage-dependent K(+) channels.
Journal Article (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
- PMC2650729
Electronic International Standard Serial Number (EISSN)
- 1545-7885
Digital Object Identifier (DOI)
- 10.1371/journal.pbio.1000047
Language
- eng
Conference Location
- United States