Structure of the Agonist-Binding Sites of theTorpedoNicotinic Acetylcholine Receptor:  Affinity-Labeling and Mutational Analyses Identify γTyr-111/δArg-113 as Antagonist Affinity Determinants†

Biochemistry ◽  
1999 ◽  
Vol 38 (20) ◽  
pp. 6689-6698 ◽  
Author(s):  
David C. Chiara ◽  
Yu Xie ◽  
Jonathan B. Cohen
Keyword(s):  
Acetylcholine Receptor ◽  
Binding Sites ◽  
Affinity Labeling ◽  
Agonist Binding ◽  
Receptor Affinity

scholarly journals Molecular blueprint of allosteric binding sites in a homologue of the agonist-binding domain of the α7 nicotinic acetylcholine receptor

2015 ◽  
Vol 112 (19) ◽  
pp. E2543-E2552 ◽  
Author(s):  
Radovan Spurny ◽  
Sarah Debaveye ◽  
Ana Farinha ◽  
Ken Veys ◽  
Ann M. Vos ◽  
...  
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Binding Sites ◽  
Agonist Binding ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Α7 Nachr ◽  
Allosteric Binding Sites ◽  
Α Helix

The α7 nicotinic acetylcholine receptor (nAChR) belongs to the family of pentameric ligand-gated ion channels and is involved in fast synaptic signaling. In this study, we take advantage of a recently identified chimera of the extracellular domain of the native α7 nicotinic acetylcholine receptor and acetylcholine binding protein, termed α7-AChBP. This chimeric receptor was used to conduct an innovative fragment-library screening in combination with X-ray crystallography to identify allosteric binding sites. One allosteric site is surface-exposed and is located near the N-terminal α-helix of the extracellular domain. Ligand binding at this site causes a conformational change of the α-helix as the fragment wedges between the α-helix and a loop homologous to the main immunogenic region of the muscle α1 subunit. A second site is located in the vestibule of the receptor, in a preexisting intrasubunit pocket opposite the agonist binding site and corresponds to a previously identified site involved in positive allosteric modulation of the bacterial homolog ELIC. A third site is located at a pocket right below the agonist binding site. Using electrophysiological recordings on the human α7 nAChR we demonstrate that the identified fragments, which bind at these sites, can modulate receptor activation. This work presents a structural framework for different allosteric binding sites in the α7 nAChR and paves the way for future development of novel allosteric modulators with therapeutic potential.

scholarly journals Analysis of agonist binding sites of muscarinic acetylcholine receptor

1983 ◽  
Vol 33 ◽  
pp. 286
Author(s):  
Atsushi Mizushima ◽  
Kazuo Matsumoto ◽  
Takeshi Osugi ◽  
Shuji Uchida ◽  
Hiroshi Yoshida
Keyword(s):  
Acetylcholine Receptor ◽  
Binding Sites ◽  
Muscarinic Acetylcholine Receptor ◽  
Agonist Binding ◽  
Muscarinic Acetylcholine
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