1hje

Structural highlights

Function

CA1_CONST Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them (PubMed:3196703). Is active on muscle nAChR (IC(50)=113 nM on adult subtype (alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND) and IC(50)=142 nM on fetal subtype (alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE)) (PubMed:35357806, PubMed:9174364). On mice muscle receptors, its higher affinity site is the alpha/delta nAChR subunit interface (PubMed:9174364). On Torpedo receptors, it does not distinguish between alpha/delta and alpha/gamma acetylcholine-binding sites (PubMed:9174364). In vivo, causes paralysis followed by death when injected into goldfish (PubMed:3196703). In contrast, has no effect on mice, when similar doses are intraperitoneally or intracerebrally injected (PubMed:3196703).^{[1] [2] [3]}

References

1. ↑ Zafaralla GC, Ramilo C, Gray WR, Karlstrom R, Olivera BM, Cruz LJ. Phylogenetic specificity of cholinergic ligands: alpha-conotoxin SI. Biochemistry. 1988 Sep 6;27(18):7102-5. PMID:3196703 doi:10.1021/bi00418a065
2. ↑ Wilhelm P, Luna-Ramirez K, Chin YK, Dekan Z, Abraham N, Tae HS, Chow CY, Eagles DA, King GF, Lewis RJ, Adams DJ, Alewood PF. Cysteine-Rich α-Conotoxin SII Displays Novel Interactions at the Muscle Nicotinic Acetylcholine Receptor. ACS Chem Neurosci. 2022 Apr 20;13(8):1245-1250. PMID:35357806 doi:10.1021/acschemneuro.1c00857
3. ↑ Groebe DR, Gray WR, Abramson SN. Determinants involved in the affinity of alpha-conotoxins GI and SI for the muscle subtype of nicotinic acetylcholine receptors. Biochemistry. 1997 May 27;36(21):6469-74. PMID:9174364 doi:10.1021/bi970195w