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XB-ART-46118
Proc Natl Acad Sci U S A May 29, 2012; 109 (22): 8552-7.

Tracking a complete voltage-sensor cycle with metal-ion bridges.

Henrion U , Renhorn J , Börjesson SI , Nelson EM , Schwaiger CS , Bjelkmar P , Wallner B , Lindahl E , Elinder F .


Abstract
Voltage-gated ion channels open and close in response to changes in membrane potential, thereby enabling electrical signaling in excitable cells. The voltage sensitivity is conferred through four voltage-sensor domains (VSDs) where positively charged residues in the fourth transmembrane segment (S4) sense the potential. While an open state is known from the Kv1.2/2.1 X-ray structure, the conformational changes underlying voltage sensing have not been resolved. We present 20 additional interactions in one open and four different closed conformations based on metal-ion bridges between all four segments of the VSD in the voltage-gated Shaker K channel. A subset of the experimental constraints was used to generate Rosetta models of the conformations that were subjected to molecular simulation and tested against the remaining constraints. This achieves a detailed model of intermediate conformations during VSD gating. The results provide molecular insight into the transition, suggesting that S4 slides at least 12 Å along its axis to open the channel with a 3(10) helix region present that moves in sequence in S4 in order to occupy the same position in space opposite F290 from open through the three first closed states.

PubMed ID: 22538811
PMC ID: PMC3365220
Article link: Proc Natl Acad Sci U S A



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