The relative orientation of the TM3 and TM4 domains varies between α1 and α3 glycine receptors

Han, Lu, Talwar, Sahil and Lynch, Joseph W. (2013) The relative orientation of the TM3 and TM4 domains varies between α1 and α3 glycine receptors. ACS Chemical Neuroscience, 4 2: 248-254. doi:10.1021/cn300177g

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ295305_postprint.pdf Full text (open access) application/pdf 3.65MB 17

Author Han, Lu
Talwar, Sahil
Lynch, Joseph W.
Title The relative orientation of the TM3 and TM4 domains varies between α1 and α3 glycine receptors
Journal name ACS Chemical Neuroscience   Check publisher's open access policy
ISSN 1948-7193
Publication date 2013-02
Year available 2012
Sub-type Article (original research)
DOI 10.1021/cn300177g
Open Access Status File (Author Post-print)
Volume 4
Issue 2
Start page 248
End page 254
Total pages 7
Place of publication Washington, DC, United States
Publisher American Chemical Society
Collection year 2013
Language eng
Abstract Glycine receptors (GlyRs) are anion-conducting members of the pentameric ligand-gated ion channel family. We previously showed that the dramatic difference in glycine efficacies of α1 and α3 GlyRs is largely attributable to their nonconserved TM4 domains. Because mutation of individual nonconserved TM4 residues had little effect, we concluded that the efficacy difference was a distributed effect of all nonconserved TM4 residues. We therefore hypothesized that the TM4 domains of α1 and α3 GlyRs differ in structure, membrane orientation, and/or molecular dynamic properties. Here we employed voltage-clamp fluorometry to test whether their TM4 domains interact differently with their respective TM3 domains. We found a rhodamine fluorophore covalently attached to a homologous TM4 residue in each receptor interacts differentially with a conserved TM3 residue. We conclude that the α1 and α3 GlyR TM4 domains are orientated differently relative to their TM3 domains. This may underlie their differential ability to influence glycine efficacy.
Keyword Binding site
pLGIC
Cys-loop receptor
Voltage clamp
Fluorescence
Mutagenesis
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published: November 26, 2012

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2013 Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 31 Mar 2013, 00:13:06 EST by System User on behalf of Queensland Brain Institute