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]
Publication Abstract from PubMed
The nuclear magnetic resonance solution structure of alpha-conotoxin SI has been determined at pH 4.2. The 36 lowest energy structures show that alpha-conotoxin SI exists in a single major solution conformation and is stabilized by six hydrogen bonds. Comparisons are made between the SI solution structure and the solution and crystal structures of alpha-conotoxin GI. Surprisingly, a high degree of similarity between the backbone conformations of the GI crystal and the SI solution structures is seen in the region of lowest sequence homology, namely residues Gly-8 to Ser-12. This similarity is more surprising when considering that in SI a proline replaces the Arg-9 found in GI. The correspondence in conformation in this region provides the definitive evidence that it is the loss of the arginine basic charge at residue 9 which determines the differences in toxicity between GI and SI, rather than any changes in conformation induced by the cyclic proline residue.
Solution structure of alpha-conotoxin SI.,Benie AJ, Whitford D, Hargittai B, Barany G, Janes RW FEBS Lett. 2000 Jul 7;476(3):287-95. PMID:10913630[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Benie AJ, Whitford D, Hargittai B, Barany G, Janes RW. Solution structure of alpha-conotoxin SI. FEBS Lett. 2000 Jul 7;476(3):287-95. PMID:10913630
