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Tracking a complete voltage-sensor cycle with metal-ion bridges
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2012 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 22, 8552-8557 p.Article in journal (Refereed) Published
Abstract [en]

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 angstrom 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.

Place, publisher, year, edition, pages
2012. Vol. 109, no 22, 8552-8557 p.
Keyword [en]
electrophysiology, inactivation, Xenopus oocytes, voltage clamp, conformational transition
National Category
Biological Sciences
URN: urn:nbn:se:su:diva-80305DOI: 10.1073/pnas.1116938109ISI: 000304881700044OAI: diva2:553150


Available from: 2012-09-18 Created: 2012-09-17 Last updated: 2012-09-18Bibliographically approved

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Lindahl, Erik
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Department of Biochemistry and Biophysics
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