Structure-function relationships of curaremimetic neurotoxin loop 2 and of a structurally similar segment of rabies virus glycoprotein in their interaction with the nicotinic acetylcholine receptor

Journal Article · Tue Nov 12 00:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00109a020· OSTI ID:5617701

Lentz, T L ^[1]

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1. Yale Univ., New Haven, CT (United States)

Peptides corresponding to portions of curaremimetic neurotoxin loop 2 and to a structurally similar segment of rabies virus glycoprotein were synthetically modified in order to gain information on structure-function relationships of neurotoxin loop 2 interactions with the acetylcholine receptor. Binding of synthetic peptides to the acetylcholine receptor of Torpedo electric organ membranes was assessed by measuring their ability to inhibit the binding of {sup 125}I-{alpha}-bungarotoxin to the receptor. The peptides showing the highest affinity for the receptor were a peptide corresponding to the sequence of loop 2 (residues 25-44) of Ophiophagus hannah (king cobra) toxin b and the structurally similar segment of CVS rabies virus glycoprotein. These affinities were comparable to those of d-tubocurarine and suberyldicholine. These results demonstrate the importance of loop 2 in the neurotoxin interaction with the receptor. N- and C-terminal deletions of the loop 2 peptides and substitution of residues invariant or highly conserved among neurotoxins were performed in order to determine the role of individual residues in binding. Residues 25-40 are the most crucial in the interaction with the acetylcholine receptor. Since this region of the glycoprotein contains residues corresponding to all of the functionally invariant neurotoxin residues, it may interact with the acetylcholine receptor through a mechanism similar to that of the neurotoxins.

• OSTI ID: 5617701
• Journal Information: Biochemistry; (United States), Vol. 30:45; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
NEUROREGULATORS
STRUCTURE-ACTIVITY RELATIONSHIPS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
ACETYLCHOLINE
GLYCOPROTEINS
RABIES
TOXINS
AMINES
AMMONIUM COMPOUNDS
ANTIGENS
AUTONOMIC NERVOUS SYSTEM AGENTS
DISEASES
DRUGS
ESTERS
HAZARDOUS MATERIALS
INFECTIOUS DISEASES
KINETICS
MATERIALS
MEMBRANE PROTEINS
NERVOUS SYSTEM DISEASES
ORGANIC COMPOUNDS
PARASYMPATHOMIMETICS
PROTEINS
QUATERNARY COMPOUNDS
REACTION KINETICS
TOXIC MATERIALS
VIRAL DISEASES
550201* - Biochemistry- Tracer Techniques