scholarly journals Profile of the α-bungarotoxin-binding regions on the extracellular part of the α-chain of Torpedo californica acetylcholine receptor

1987 ◽  
Vol 248 (3) ◽  
pp. 847-852 ◽  
Author(s):  
B MULAC-JERIČEVIČ ◽  
M Z Atassi
Keyword(s):  
Acetylcholine Receptor ◽  
Torpedo Californica ◽  
Alpha Chain ◽  
Toxin Binding ◽  
The Third ◽  
Binding Regions ◽  
Α Chain ◽  
Alpha Bungarotoxin ◽  
Receptor Antibodies ◽  
Anti Acetylcholine

The continuous alpha-neurotoxin-binding regions on the extracellular part (residues 1-210) of the alpha-chain of Torpedo californica acetylcholine receptor were localized by reaction of 125I-labelled alpha-bungarotoxin with synthetic overlapping peptides spanning this entire part of the chain. The specificity of the binding was confirmed by inhibition with unlabelled toxin and, for appropriate peptides, with unlabelled anti-(acetylcholine receptor) antibodies. Five toxin-binding regions were localized within residues 1-10, 32-41, 100-115, 122-150 and 182-198. The third, fourth and fifth (and to a lesser extent the first and second) toxin-binding regions overlapped with regions recognized by anti-(acetylcholine receptor) antibodies. The five toxin-binding regions may be distinct sites or, alternatively, different ‘faces’ in one (or more) sites.

Detection and characterization of blocking-type anti-acetylcholine receptor antibodies in sera from patients with myasthenia gravis

1993 ◽  
Vol 39 (10) ◽  
pp. 2053-2057 ◽  
Author(s):  
H Hara ◽  
K Hayashi ◽  
K Ohta ◽  
N Itoh ◽  
H Nishitani ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Highly Sensitive ◽  
Direct Binding ◽  
Inhibitory Activities ◽  
Alpha Bungarotoxin ◽  
Receptor Antibodies ◽  
Blocking Type ◽  
Anti Acetylcholine

Abstract We developed a highly sensitive, convenient assay for measuring blocking-type anti-acetylcholine receptor antibodies, which inhibit the binding of 125I-labeled alpha-bungarotoxin (alpha-BuTx) to the acetylcholine receptor (AChR). This procedure detected inhibitory activities in sera from 76% of patients with myasthenia gravis. Results of an experiment done with synthetic peptide corresponding to the alpha-BuTx binding region in the alpha-subunit of Torpedo AChR suggested that this inhibition is due to nonspecific steric hindrance caused by the binding of antibodies to a region other than the alpha-BuTx site, rather than by direct binding to the latter site. The inhibitory activities of the blocking-type antibodies and the titers of non-blocking-type antibodies were correlated. Moreover, the blocking-type antibodies could dissociate 125I-labeled alpha-BuTx from 125I-labeled alpha-BuTx-human AChR complex, and their dissociation activities showed good correlation with the inhibitory activities.

scholarly journals The short-neurotoxin-binding regions on the α-chain of human and Torpedo californica acetylcholine receptors

1991 ◽  
Vol 274 (3) ◽  
pp. 849-854 ◽  
Author(s):  
K H Ruan ◽  
B G Stiles ◽  
M Z Atassi
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptors ◽  
Binding Activity ◽  
Lower Activity ◽  
Binding Region ◽  
Torpedo Californica ◽  
Binding Regions ◽  
Alpha Bungarotoxin ◽  
Erabutoxin B ◽  
Low Activity

The continuous regions for short-neurotoxin binding on the alpha-chains of Torpedo californica (electric ray) and human acetylcholine receptors (AChR) were localized by reaction of 125I-labelled cobrotoxin (Cot) and erabutoxin b (Eb) with synthetic overlapping peptides spanning the entire extracellular part of the respective alpha-chains. On Torpedo AChR, five Cot-binding regions were found to reside within peptides alpha 1-16, alpha 23-38/alpha 34-49 overlap, alpha 100-115, alpha 122-138 and alpha 194-210. The Eb-binding regions were localized within peptides alpha 23-38/alpha 34-49/alpha 45-60 overlap, alpha 100-115 and alpha 122-138. The main binding activity for both toxins resided within region alpha 122-138. In previous studies we had shown that the binding of long alpha-neurotoxins [alpha-bungarotoxin (Bgt) and cobratoxin (Cbt)] involved the same regions on Torpedo AChR as well as an additional region within residues alpha 182-198. Thus region alpha 182-198, which is the strongest binding region for long neurotoxins on Torpedo AChR, was not a binding region for short neurotoxins. On human AChR, peptide alpha 122-138 possessed the highest activity with both toxins, and lower activity was found in the overlap alpha 23-38/alpha 34-49/alpha 45-60 and in peptide alpha 194-210. In addition, peptides alpha 100-115 and alpha 56-71 showed strong and medium binding activities to Eb, but low activity to Cot, whereas peptide alpha 1-16 exhibited low binding to Cot and no binding to Eb. Comparison with previous studies indicated that, for human AChR, the binding regions of short and long neurotoxins were essentially the same. The finding that the region within residues alpha 122-138 of both human and Torpedo AChR possessed the highest binding activity with short neurotoxins indicated that this region constitutes a universal binding site for long and short neurotoxins on AChR from various species.

Anti-acetylcholine receptor antibodies in neonatal myasthenia gravis: Heterogeneity and pathogenic significance

1991 ◽  
Vol 4 (2) ◽  
pp. 185-195 ◽  
Author(s):  
Bruno Eymard ◽  
Béatrice Vernet-der Garabedian ◽  
Sonia Berrih-Aknin ◽  
Claude Pannier ◽  
Jean-François Bach ◽  
...  
Keyword(s):  
Myasthenia Gravis ◽  
Acetylcholine Receptor ◽  
Receptor Antibodies ◽  
Anti Acetylcholine
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