Reorganization of the nicotinic acetylcholine receptor during desensitization probed with a photoactivatable agonist.
The nicotinic acetylcholine receptor (nAChR) from fish electric organs and vertebrate neuromuscular junctions is a well-characterized transmembrane allosteric protein, composed of four polypeptide chains assembled into a heterologous pentamer alpha2betagammadelta, which carries ACh-binding sites and contains cation-selective channel-forming elements. Topographical mapping of residues contributing to the ligand-binding domain (LBD) of Torpedo nAChR was achieved with different site-directed antagonist or agonist probes. Over two decades of biochemical investigation led to the identification of three discontinuous domains on alpha subunits, with additional residues on gamma and delta subunits (Kotzyba- Hibert et al., 2004). This six binding-segment-domain model fits quite nicely with the three-dimensional positioning of the homologous residues in AChbinding protein (Brejc et al., 2001). However, little is known about the structural dynamics of the functioning receptor.
Mourot
Alexandre
A
UMR 7514 CNRS, Université Louis Pasteur Strasbourg, BP 24, 67401 Illkirch Cedex, France. alexandre.mourot@mpibp-frankfurt.mpg.de
Rodrigo
J
J
Bertrand
Sonia
S
Bertrand
Daniel
D
Goeldner
Maurice
M
Kotzyba-Hibert
Florence
F
D000345:Affinity Labels; D000818:Animals; D001665:Binding Sites; D003979:Diazonium Compounds / Q000494:pharmacology; D004557:Electric Organ / Q000502:physiology*; D008024:Ligands; D009469:Neuromuscular Junction / Q000502:physiology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D019920:Photoaffinity Labels / Q000494:pharmacology; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D014101:Torpedo; D014714:Vertebrates
D000345:Affinity Labels; D003979:Diazonium Compounds; D008024:Ligands; D018722:Nicotinic Agonists; D010671:Phenylurea Compounds; D019920:Photoaffinity Labels; D011978:Receptors, Nicotinic; C075309:(N'-methyl,N'-4-diazonium phenyl)(N-6-hexanoic acid, 2-(trimethylammonium)ethyl ester)urea