Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery

Talwar, Sahil and Lynch, Joseph W. (2014) Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery. International Journal of Biochemistry and Cell Biology, 53 218-233. doi:10.1016/j.biocel.2014.05.028

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Author Talwar, Sahil
Lynch, Joseph W.
Title Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery
Journal name International Journal of Biochemistry and Cell Biology   Check publisher's open access policy
ISSN 1357-2725
1878-5875
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.biocel.2014.05.028
Open Access Status File (Author Post-print)
Volume 53
Start page 218
End page 233
Total pages 16
Place of publication Cambridge, MA United States
Publisher Elsevier Ltd
Language eng
Subject 1303 Specialist Studies in Education
1307 Cell Biology
Abstract Pentameric ligand-gated ion channels (pLGICs) mediate numerous physiological processes, including fast neurotransmission in the brain. They are targeted by a large number of clinically-important drugs and disruptions to their function are associated with many neurological disorders. The phosphorylation of pLGICs can result in a wide range of functional consequences. Indeed, many neurological disorders result from pLGIC phosphorylation. For example, chronic pain is caused by the protein kinase A-mediated phosphorylation of α3 glycine receptors and nicotine addiction is mediated by the phosphorylation of α4- or α7-containing nicotinic receptors. A recent study demonstrated that phosphorylation can induce a global conformational change in a pLGIC that propagates to the neurotransmitter-binding site. Here we present evidence that phosphorylation-induced global conformational changes may be a universal phenomenon in pLGICs. This raises the possibility of designing drugs to specifically treat disease-modified pLGICs. This review summarizes some of the opportunities available in this area.
Keyword Conformational changes
Cys-loop receptor
Drug discovery
Pentameric ligand-gated ion channel
Phosphorylation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Biomedical Sciences Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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