Abstract: | A series of neurotoxin II (Naja naja oxiana) derivatives, each containing one p-azido-[14C]benzoyl group, have been prepared. Those labeled at Leu1, Lys15, Lys25, Lys26, or Lys46 associate specifically with the acetylcholine receptor from the Torpedo marmorata electric organs and form the crosslinks with it as a result of irradiation. Electrophoresis in polyacrylamide gel and gel chromatography revealed the contacts between the neurotoxins and alpha, beta, gamma and delta subunits of the receptor, modification of a particular subunit being governed by the photoactivable group position in the neurotoxin molecule. The differences of the two neurotoxin binding sites in the receptor were demonstrated by analysis of the photoinduced crosslinks under the conditions of one site being blocked by hexa (trifluoroacetyl) neurotoxin II. The mutual arrangement of the two bound neurotoxin molecules was established. On the basis of data obtained, two models for the acetylcholine receptor subunit topography were proposed. |