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Tracking a complete...
Tracking a complete voltage-sensor cycle with metal-ion bridges
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- Henrion, Ulrike (author)
- Linköpings universitet,Hälsouniversitetet,Avdelningen för cellbiologi
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- Renhorn, Jakob (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Börjesson, Sara (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Nelson, Erin M (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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- Schwaiger, Christine S. (author)
- KTH,Beräkningsbiofysik,Royal Institute of Technology, Sweden
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- Bjelkmar, Pär (author)
- KTH,Stockholms universitet,Institutionen för biokemi och biofysik,Beräkningsbiofysik,Royal Institute of Technology, Sweden Stockholm University, Sweden
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- Wallner, Björn (author)
- Linköpings universitet,Bioinformatik,Tekniska högskolan
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- Lindahl, Erik (author)
- KTH,Stockholms universitet,Institutionen för biokemi och biofysik,Beräkningsbiofysik,Royal Institute of Technology, Sweden Stockholm University, Sweden
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- Elinder, Fredrik (author)
- Linköpings universitet,Cellbiologi,Hälsouniversitetet
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(creator_code:org_t)
- 2012-04-25
- 2012
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:22, s. 8552-8557
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Abstract
Subject headings
Close
- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Fysik -- Annan fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences -- Other Physics Topics (hsv//eng)
Keyword
- electrophysiology
- inactivation
- Xenopus oocytes
- voltage clamp
- conformational transition
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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