Cysteine-Rich α-Conotoxin SII Displays Novel Interactions at the Muscle Nicotinic Acetylcholine Receptor.

Autor:	Wilhelm P; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia., Luna-Ramirez K; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, NSW 2522, Australia., Chin YK; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.; Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD 4072, Australia., Dekan Z; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia., Abraham N; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia., Tae HS; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, NSW 2522, Australia., Chow CY; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia., Eagles DA; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia., King GF; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia., Lewis RJ; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia., Adams DJ; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, NSW 2522, Australia., Alewood PF; Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD 4072, Australia.
Jazyk:	angličtina
Zdroj:	ACS chemical neuroscience [ACS Chem Neurosci] 2022 Apr 20; Vol. 13 (8), pp. 1245-1250. Date of Electronic Publication: 2022 Mar 31.
DOI:	10.1021/acschemneuro.1c00857
Abstrakt:	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 3 10 -helix frequently employed by framework I α-conotoxins; α-SII acted at the muscle nAChR with half-maximal inhibitory concentrations (IC 50 ) 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu