Mapping the main immunogenic region and toxin-binding site of the nicotinic acetylcholine receptor

Science ◽  
1987 ◽  
Vol 235 (4784) ◽  
pp. 77-80 ◽  
Author(s):  
T Barkas ◽  
A Mauron ◽  
B Roth ◽  
C Alliod ◽  
S. Tzartos ◽  
...  
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Toxin Binding ◽  
Immunogenic Region

Neuronal nicotinic α-bungarotoxin sites

1988 ◽  
Vol 66 (7) ◽  
pp. 971-979 ◽  
Author(s):  
M. Quik ◽  
S. Geertsen
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Receptor ◽  
Experimental Studies ◽  
Cellular Functions ◽  
Nicotinic Acetylcholine ◽  
Toxin Binding ◽  
Neuronal Tissues ◽  
Tightly Coupled

At the vertebrate neuromuscular junction and in the electroplax of eel and electric fish, the nicotinic α-bungarotoxin site and the nicotinic receptor involved in synaptic transmission are very tightly coupled and, indeed, appear to be the same molecular component. On the other hand, the nature of the relationship between the nicotinic receptor mediating synaptic events and the nicotinic α-bungarotoxin binding site in nervous tissue has been a matter of controversy over the last few years. Experimental studies have been accumulating which suggest that in many neuronal tissues these two components are distinct molecular entities with their own unique regulation. However, it also appears that in other nervous tissues, possibly in species lower on the evolutionary scale, the toxin binding site is part of the nicotinic receptor. An evaluation of all available evidence would point to the conclusion that, in neuronal tissues, the nicotinic acetylcholine receptor involved in synaptic events and the nicotinic α-bungarotoxin site can exist both in a tightly coupled form and one in which the two sites are mutually distinct. The possible physiological significance of the nicotinic α-bungarotoxin site is discussed in light of current experimental data. Evidence is available which may imply that the α-toxin site, whether it is present as a distinct entity or in association with the nicotinic acetylcholine receptor, is involved in trophic or growth related activities, as well as in other cellular functions. The possibility of an endogenous ligand for the nicotinic α-bungarotoxin site is also discussed.

scholarly journals Identification of regions involved in the binding of alpha-bungarotoxin to the human alpha7 neuronal nicotinic acetylcholine receptor using synthetic peptides

2003 ◽  
Vol 372 (2) ◽  
pp. 543-554 ◽  
Author(s):  
Martha MARINOU ◽  
Socrates J. TZARTOS
Keyword(s):  
Binding Site ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Binding Sites ◽  
Synthetic Peptides ◽  
Extracellular Domain ◽  
Muscle Type ◽  
Nicotinic Acetylcholine ◽  
Toxin Binding ◽  
Α1 Subunit

The neuronal α7 nicotinic acetylcholine receptor (AChR) binds the neurotoxin α-bungarotoxin (α-Bgt). Fine mapping of the α-Bgt-binding site on the human α7 AChR was performed using synthetic peptides covering the entire extracellular domain of the human α7 subunit (residues 1–206). Screening of these peptides for 125I-α-Bgt binding resulted in the identification of at least two toxin-binding sites, one at residues 186–197, which exhibited the best 125I-α-Bgt binding, and one at residues 159–165, with weak toxin-binding capacity; these correspond, respectively, to loops C and IV of the agonist-binding site. Toxin binding to the α7(186–197) peptide was almost completely inhibited by unlabelled α-Bgt or d-tubocurarine. Alanine substitutions within the sequence 186–198 revealed a predominant contribution of aromatic and negatively charged residues to the binding site. This sequence is homologous to the α-Bgt binding site of the α1 subunit (residues 188–200 in Torpedo AChR). In competition experiments, the soluble peptides α7(186–197) and Torpedo α1(184–200) inhibited the binding of 125I-α-Bgt to the immobilized α7(186–197) peptide, to native Torpedo AChR, and to the extracellular domain of the human α1 subunit. These results suggest that the toxin-binding sites of the neuronal α7 and muscle-type AChRs bind to identical or overlapping sites on the α-Bgt molecule. In support of this, when synthetic α-Bgt peptides were tested for binding to the recombinant extracellular domains of the human α7 and α1 subunits, and to native Torpedo and α7 AChR, the results indicated that α-Bgt interacts with both neuronal and muscle-type AChRs through its central loop II and C-terminal tail.

Sign in / Sign up

Export Citation Format

Share Document