title: Fourier transform infrared (FTIR) spectroscopic investigation of the nicotinic acetylcholine receptor (nAChR). Investigation of agonist binding and receptor conformational changes by flash-induced release of 'caged' carbamoylcholine.
abstract: The binding and interaction of carbamoylcholine with the nicotinic acetylcholine receptor was investigated using photolytically released carbamoylcholine ('caged' carbamoylcholine). Upon UV flash activation of this photolabile substrate analog, characteristic changes in the IR absorbance spectrum were detected. Apart from difference bands arising from the changes of molecular structure upon photolytical release, spectral features can be attributed to the agonist upon binding to the receptor as well as to conformational changes of the receptor itself. The two photo-labile agonist analogs N-[1-(2-nitrophenyl)ethyl] carbamoylcholine iodide (cage I) and N-(alpha-carboxy-2-nitrobenzyl) carbamoylcholine trifluoroacetate (cage II), with different structures for comparison of the 1680-1540 cm-1 region sensitive for protein conformation, yielded consistent results. A preliminary interpretation in terms of substrate binding and local conformational changes of the receptor upon carbamoylcholine binding is provided, in analogy to the binding of acetylcholine, activation, and subsequent deactivation taking place during signal transduction.
authors.affiliation: Institut für Biochemie, Freie Universität Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Görne-Tschelnokow
authors.forename: F
authors.initials: F
authors.lastname: Hucho
authors.forename: D
authors.initials: D
authors.lastname: Naumann
authors.forename: A
authors.initials: A
authors.lastname: Barth
authors.forename: W
authors.initials: W
authors.lastname: Mäntele
mesh_terms: D000818:Animals; D002217:Carbachol / Q000378:metabolism*; D005583:Fourier Analysis; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D013055:Spectrophotometry, Infrared; D014101:Torpedo
chemical_list: D011978:Receptors, Nicotinic; D002217:Carbachol