Alanine-Scanning Mutagenesis of α-Conotoxin GI Reveals the Residues Crucial for Activity at the Muscle Acetylcholine Receptor.

ABSTRACT: Recently, the muscle-type nicotinic acetylcholine receptors (nAChRs) have been pursued as a potential target of several diseases, including myogenic disorders, muscle dystrophies and myasthenia gravis, etc. α-conotoxin GI isolated from Conus geographus selectively and potently inhibited the muscle-type nAChRs which can be developed as a tool to study them. Herein, alanine scanning mutagenesis was used to reveal the structure⁻activity relationship (SAR) between GI and mouse α1β1δε nAChRs. The Pro⁵, Gly⁸, Arg⁸, and Tyr¹¹ were proved to be the critical residues for receptor inhibiting as the alanine (Ala) replacement led to a significant potency loss on mouse α1β1δε nAChR. On the contrary, substituting Asn⁴, His¹⁰ and Ser¹² with Ala respectively did not

SUBMITTER: Ning J 

PROVIDER: S-EPMC6315591 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature