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

By Sahil Talwar and Joseph W. Lynch


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

Topics: Conformational changes, Cys-loop receptor, Drug discovery, Pentameric ligand-gated ion channel, Phosphorylation, 1303 Specialist Studies in Education, 1307 Cell Biology
Publisher: Elsevier Ltd
Year: 2014
DOI identifier: 10.1016/j.biocel.2014.05.028
OAI identifier:

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