Selective loss of binding sites for the iodinated alpha-neurotoxin I from Naja mossambica mossambica venom upon enzymatic deglycosylation of Torpedo electric organ membranes

Eur J Biochem. 1988 Jun 15;174(3):543-50. doi: 10.1111/j.1432-1033.1988.tb14133.x.

Abstract

Removal of asparagine-linked carbohydrate chains from Torpedo marmorata electric organ membranes was found to inhibit the binding of the iodinated alpha-neurotoxin I from Naja mossambica mossambica snake venom to its receptor. Optimal deglycosylation of membranes by endoglycosidase F resulted in a 55% inhibition of alpha-neurotoxin-I-saturable binding. Under these conditions, up to 70% of concanavalin A binding was also lost, indicating an efficient removal of mannose-rich carbohydrate chains. Saturation binding experiments at equilibrium on membranes incubated in the absence of endoglycosidase F indicated, when analyzed by Scatchard plots, the presence of two classes of high-affinity binding sites for alpha-neurotoxin I (kd = 9 pM and 68 pM respectively) with capacities of 24 and 14 pmol/mg membrane proteins, respectively. After endoglycosidase F treatment, only the former class of binding sites (Kd = 11 pM) was recovered together with a 45% reduction in the number of total binding sites. Dissociation experiments further confirmed the presence of two types of toxin-receptor complexes in control membranes and the selective loss of the rapidly dissociating component upon deglycosylation. The binding of alpha-neurotoxin I to its receptor, deglycosylated or not, was totally inhibited by carbamoylcholine, d-tubocurarine or alpha-bungarotoxin. These findings show that the neurotoxin binding sites present on the acetylcholine receptor can be discriminated on the basis of their differential susceptibility to the removal of asparagine-linked carbohydrate chains.

MeSH terms

  • Animals
  • Asparagine / physiology
  • Binding Sites / drug effects
  • Binding, Competitive
  • Cobra Neurotoxin Proteins / metabolism*
  • Concanavalin A / metabolism
  • Elapid Venoms / metabolism*
  • Electric Organ / metabolism*
  • Glycoside Hydrolases / metabolism
  • Glycosylation
  • Kinetics
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
  • Membrane Proteins / analysis
  • Receptors, Cholinergic / drug effects
  • Receptors, Cholinergic / metabolism*
  • Torpedo / physiology

Substances

  • Cobra Neurotoxin Proteins
  • Elapid Venoms
  • Membrane Proteins
  • Receptors, Cholinergic
  • Concanavalin A
  • Asparagine
  • Glycoside Hydrolases
  • Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase