Publication Date:
2012-04-14
Description:
The mechanism of ion channel voltage gating-how channels open and close in response to voltage changes-has been debated since Hodgkin and Huxley's seminal discovery that the crux of nerve conduction is ion flow across cellular membranes. Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated and deactivated states. On deactivation, pore hydrophobic collapse rapidly halts ion flow. Subsequent voltage-sensing domain (VSD) relaxation, including inward, 15-angstrom S4-helix motion, completes the transition. On activation, outward S4 motion tightens the VSD-pore linker, perturbing linker-S6-helix packing. Fluctuations allow water, then potassium ions, to reenter the pore; linker-S6 repacking stabilizes the open pore. We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jensen, Morten O -- Jogini, Vishwanath -- Borhani, David W -- Leffler, Abba E -- Dror, Ron O -- Shaw, David E -- New York, N.Y. -- Science. 2012 Apr 13;336(6078):229-33. doi: 10.1126/science.1216533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉D E Shaw Research, New York, NY 10036, USA. morten.jensen@DEShawResearch.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22499946" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Hydrophobic and Hydrophilic Interactions
;
*Ion Channel Gating
;
Kv1.2 Potassium Channel/*chemistry/*metabolism
;
Membrane Potentials
;
Models, Biological
;
Models, Molecular
;
Molecular Dynamics Simulation
;
Protein Conformation
;
Protein Structure, Secondary
;
Protein Structure, Tertiary
;
Rats
;
Recombinant Fusion Proteins/chemistry/metabolism
;
Shab Potassium Channels/*chemistry/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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