Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks

Login for users with Unibas email account...

Login for registered users without Unibas email account...

 
A limited 4 a radial displacement of the s4-s5 linker is sufficient for internal gate closing in kv channels
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 1445135
Author(s) Faure, Élise; Starek, Greg; McGuire, Hugo; Bernèche, Simon; Blunck, Rikard
Author(s) at UniBasel Bernèche, Simon
Year 2012
Title A limited 4 a radial displacement of the s4-s5 linker is sufficient for internal gate closing in kv channels
Journal Journal of biological chemistry
Volume 287
Number 47
Pages / Article-Number 40091-8
Keywords Electrophysiology, Fluorescence Resonance Energy Transfer (FRET), Gating, Molecular Dynamics, Potassium Channels, LRET, Internal Gate, Lipid Regulation
Abstract

Voltage-gated ion channels are responsible for the generation of action potentials in our nervous system. Conformational rearrangements in their voltage sensor domains in response to changes of the membrane potential control pore opening and thus ion conduction. Crystal structures of the open channel in combination with a wealth of biophysical data and molecular dynamics simulations led to a consensus on the voltage sensor movement. However, the coupling between voltage sensor movement and pore opening, the electromechanical coupling, occurs at the cytosolic face of the channel, from where no structural information is available yet. In particular, the question how far the cytosolic pore gate has to close to prevent ion conduction remains controversial. In cells, spectroscopic methods are hindered because labeling of internal sites remains difficult, whereas liposomes or detergent solutions containing purified ion channels lack voltage control. Here, to overcome these problems, we controlled the state of the channel by varying the lipid environment. This way, we directly measured the position of the S4-S5 linker in both the open and the closed state of a prokaryotic Kv channel (KvAP) in a lipid environment using Lanthanide-based resonance energy transfer. We were able to reconstruct the movement of the covalent link between the voltage sensor and the pore domain and used this information as restraints for molecular dynamics simulations of the closed state structure. We found that a small decrease of the pore radius of about 3-4 Å is sufficient to prevent ion permeation through the pore.

Publisher American Society of Biological Chemists
ISSN/ISBN 0021-9258
edoc-URL http://edoc.unibas.ch/dok/A6043857
Full Text on edoc No
Digital Object Identifier DOI 10.1074/jbc.M112.415497
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/23019337
ISI-Number WOS:000311233800076
Document type (ISI) Journal Article
 
   

MCSS v5.8 PRO. 0.326 sec, queries - 0.000 sec ©Universität Basel  |  Impressum   |    
13/05/2024