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The role of Loop F in the activation of the GABA receptor
Author(s) -
Khatri Alpa,
Weiss David S.
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.179705
Subject(s) - agonist , chemistry , ligand gated ion channel , biophysics , nicotinic agonist , binding site , nicotinic acetylcholine receptor , receptor , acetylcholine receptor , loop (graph theory) , glycine receptor , ion channel , acetylcholine , cys loop receptors , glycine , stereochemistry , biochemistry , biology , pharmacology , amino acid , mathematics , combinatorics
Functional studies of the ligand gated ion channel family (nicotinic acetylcholine, serotonin Type 3, glycine and GABA receptors) along with the crystal structure of the acetylcholine binding protein (AChBP) and molecular dynamics simulations of the nAChR structure have resulted in a structural model in which the agonist‐binding pocket comprises six loops (A–F) contributed by adjacent subunits. It is presumed that the binding of agonist results in a local structural rearrangement that is then transduced to the gate, causing the pore to open. Efforts are underway to better define the specific roles of the six binding loops. Several studies have suggested Loop F may play a direct role in linking the structural rearrangement within the binding pocket to the gate, although other investigations have indicated Loop F may be crucial for locking the agonist molecule into the binding site. This review will focus on the controversy surrounding the role of Loop F during GABA receptor activation.