Functionality of nitrated acetylcholine receptor: the two-step formation of nitrotyrosines reveals their differential role in effectors binding.
The presence of nitrotyrosines is associated with several neurodegenerative pathologies. We evaluated the functionality of the nicotinic acetylcholine receptor possessing nitrotyrosines. The spectrum of the nitrated receptor displays an absorption band characteristic of ortho-nitrophenol. The presence of carbamylcholine in the agonist site prevented the effect of nitration by tetranitromethane in some conditions. The nitration occurred with two discrete steps and pointed out the differential involvement of tyrosines in the binding of acetylcholine and neurotoxin. We concluded that at least two residues involved in agonist binding can be nitrated, which bring similar contributions to the binding energy of the neurotransmitter.
Négrerie
Michel
M
INSERM U696, UMR7645, Laboratoire d'Optique et Biosciences, Ecole Polytechnique, Palaiseau, France. michel.negrerie@polytechnique.fr
Martin
Jean-Louis
JL
Nghiêm
Hoàng-Oanh
HO
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000378:metabolism; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007457:Iodine Radioisotopes / Q000378:metabolism; D007700:Kinetics; D018722:Nicotinic Agonists / Q000378:metabolism; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D013053:Spectrophotometry; D013774:Tetranitromethane / Q000378:metabolism / Q000494:pharmacology; D014101:Torpedo; D014403:Tubocurarine / Q000378:metabolism / Q000494:pharmacology; D014443:Tyrosine / Q000096:biosynthesis* / Q000235:genetics
D002038:Bungarotoxins; D002250:Carbon Radioisotopes; D007457:Iodine Radioisotopes; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014443:Tyrosine; D002217:Carbachol; D013774:Tetranitromethane; D000109:Acetylcholine; D014403:Tubocurarine