Cysteine-Rich α-Conotoxin SII Displays Novel Interactions at the Muscle Nicotinic Acetylcholine Receptor.
ACS Chem Neurosci
; 13(8): 1245-1250, 2022 04 20.
Article
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| MEDLINE
| ID: mdl-35357806
ABSTRACT
α-Conotoxins that target muscle nicotinic acetylcholine receptors (nAChRs) commonly fall into two structural classes, frameworks I and II containing two and three disulfide bonds, respectively. Conotoxin SII is the sole member of the cysteine-rich framework II with ill-defined interactions at the nAChRs. Following directed synthesis of α-SII, NMR analysis revealed a well-defined structure containing a 310-helix frequently employed by framework I α-conotoxins; α-SII acted at the muscle nAChR with half-maximal inhibitory concentrations (IC50) of 120 nM (adult) and 370 nM (fetal) though weakly at neuronal nAChRs. Truncation of α-SII to a two disulfide bond amidated peptide with framework I disulfide connectivity led to similar activity. Surprisingly, the more constrained α-SII was less stable under mild reducing conditions and displayed a unique docking mode at the nAChR.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Receptores Nicotínicos
/
Conotoxinas
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2022
Tipo del documento:
Article
País de afiliación:
Australia