Rigidity of loop 1 contributes to equipotency of globular and ribbon isomers of α-conotoxin AusIA.

ABSTRACT: α-Conotoxins are small disulfide-rich peptides targeting nicotinic acetylcholine receptors (nAChRs) characterised by a C^IC^II-X_m-C^III-X_n-C^IV framework that invariably adopt the native globular conformations which is typically most potent. α-Conotoxins are divided into several structural subgroups based on the number of residues within the two loops braced by the disulfide bonds (m/n), with the 4/7 and 4/3 subgroups dominating. AusIA is a relatively rare α5/5-conotoxin isolated from the venom of Conus australis. Surprisingly, the ribbon isomer displayed equipotency to the wild-type globular AusIA at human α7-containing nAChR. To understand the molecular basis for equipotency, we determined the co-crystal structures of both iso

SUBMITTER: Ho TNT 

PROVIDER: S-EPMC8578332 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature