liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
The Free Energy Barrier for Arginine Gating Charge Translation Is Altered by Mutations in the Voltage Sensor Domain
Science Life Lab, Sweden Royal Institute Technology, Sweden .
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0001-8493-0114
Science Life Lab, Sweden Royal Institute Technology, Sweden .
Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.ORCID iD: 0000-0002-3772-8279
Show others and affiliations
2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 10, E45880- p.Article in journal (Refereed) Published
Abstract [en]

The gating of voltage-gated ion channels is controlled by the arginine-rich S4 helix of the voltage-sensor domain moving in response to an external potential. Recent studies have suggested that S4 moves in three to four steps to open the conducting pore, thus visiting several intermediate conformations during gating. However, the exact conformational changes are not known in detail. For instance, it has been suggested that there is a local rotation in the helix corresponding to short segments of a 3(10)-helix moving along S4 during opening and closing. Here, we have explored the energetics of the transition between the fully open state (based on the X-ray structure) and the first intermediate state towards channel closing (C-1), modeled from experimental constraints. We show that conformations within 3 angstrom of the X-ray structure are obtained in simulations starting from the C-1 model, and directly observe the previously suggested sliding 3(10)-helix region in S4. Through systematic free energy calculations, we show that the C-1 state is a stable intermediate conformation and determine free energy profiles for moving between the states without constraints. Mutations indicate several residues in a narrow hydrophobic band in the voltage sensor contribute to the barrier between the open and C-1 states, with F233 in the S2 helix having the largest influence. Substitution for smaller amino acids reduces the transition cost, while introduction of a larger ring increases it, largely confirming experimental activation shift results. There is a systematic correlation between the local aromatic ring rotation, the arginine barrier crossing, and the corresponding relative free energy. In particular, it appears to be more advantageous for the F233 side chain to rotate towards the extracellular side when arginines cross the hydrophobic region.

Place, publisher, year, edition, pages
Public Library of Science , 2012. Vol. 7, no 10, E45880- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-85629DOI: 10.1371/journal.pone.0045880ISI: 000310050200005OAI: diva2:572057

Funding Agencies|European Research Council|209825|Vetenskapsradet|2010-5107|Swedish Foundation for Strategic Research||Swedish e-Science Research Center||

Available from: 2012-11-26 Created: 2012-11-26 Last updated: 2013-10-15

Open Access in DiVA

fulltext(1799 kB)122 downloads
File information
File name FULLTEXT01.pdfFile size 1799 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Börjesson, SaraWallner, BjörnElinder, Fredrik
By organisation
Cell BiologyFaculty of Health SciencesBioinformaticsThe Institute of Technology
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 122 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 27 hits
ReferencesLink to record
Permanent link

Direct link