| Molecular dynamics simulations of the Cx26 hemichannel: insights into voltage-dependent loop-gating. | |
| | |
MedLine Citation:
|
PMID: 22455917 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Loop-gating is one of two voltage-dependent mechanisms that regulate the open probability of connexin channels. The loop-gate permeability barrier is formed by a segment of the first extracellular loop (E1) (the parahelix) and appears to be accompanied by straightening of the bend angle between E1 and the first transmembrane domain (TM1). Here, all-atom molecular dynamics simulations are used to identify and characterize interacting van der Waals and electrostatic networks that stabilize the parahelices and TM1/E1 bend angles of the open Cx26 hemichannel. Dynamic fluctuations in an electrostatic network in each subunit are directly linked to the stability of parahelix structure and TM1/E1 bend angle in adjacent subunits. The electrostatic network includes charged residues that are pore-lining and thus positioned to be voltage sensors. We propose that the transition to the closed state is initiated by voltage-driven disruption of the networks that stabilize the open-state parahelix configuration, allowing the parahelix to protrude into the channel pore to form the loop-gate barrier. Straightening of the TM1/E1 bend appears to be a consequence of the reorganization of the interacting networks that accompany the conformational change of the parahelix. The electrostatic network extends across subunit boundaries, suggesting a concerted gating mechanism. |
| | |
Authors:
|
Taekyung Kwon; Benoît Roux; Sunhwan Jo; Jeffery B Klauda; Andrew L Harris; Thaddeus A Bargiello |
Related Documents
:
|
22845837 - Conformational dynamics of hiv-1 protease: a comparative molecular dynamics simulation ... 22660127 - Fast and highly accurate boundary element method for scattering calculation of defectiv... 20652137 - Rapid concentration of nanoparticles with dc dielectrophoresis in focused electric fields. 22324707 - Why nanoprojectiles work differently than macroimpactors: the role of plastic flow. 17930377 - Pairing and density-wave phases in boson-fermion mixtures at fixed filling. 18643167 - Multicomponent and multiphase modeling and simulation of reactive wetting. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-03-20 |
Journal Detail:
|
Title: Biophysical journal Volume: 102 ISSN: 1542-0086 ISO Abbreviation: Biophys. J. Publication Date: 2012 Mar |
Date Detail:
|
Created Date: 2012-03-29 Completed Date: 2012-08-02 Revised Date: 2013-05-20 |
Medline Journal Info:
|
Nlm Unique ID: 0370626 Medline TA: Biophys J Country: United States |
Other Details:
|
Languages: eng Pagination: 1341-51 Citation Subset: IM |
Copyright Information:
|
Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved. |
Affiliation:
|
Dominic P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Substitution Amino Acids / metabolism Connexins / chemistry*, metabolism* Ion Channel Gating* Ion Channels / chemistry*, metabolism* Molecular Dynamics Simulation* Mutation / genetics Permeability Protein Structure, Secondary Protein Structure, Tertiary Protein Subunits / chemistry, metabolism Static Electricity |
| Grant Support | |
ID/Acronym/Agency:
|
R01 GM062342/GM/NIGMS NIH HHS; R01 GM062342/GM/NIGMS NIH HHS; R01 GM064889/GM/NIGMS NIH HHS; R01 NS056509/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Amino Acids; 0/Connexins; 0/Ion Channels; 0/Protein Subunits; 127120-53-0/connexin 26 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Constraints imposed by the membrane selectively guide the alternating access dynamics of the glutama...
Next Document: Applicability of cable theory to vascular conducted responses.