8.B.32. The Nicotinic Acetylcholine Receptor-targeting Alpha-Conotoxin (A-Conotoxin) Family
α-Conotoxins bind to neuronal and muscular nicotinic acetylcholine receptors (nAChR) and inhibit them. These toxins block neuronal mammalian nAChRs (alpha-6/alpha-3-beta-2-beta-3 (0.39 nM) > alpha-3-beta-2 > alpha-3-beta-4 = alpha-4-beta-2) (Cartier et al. 1996; Kuryatov et al. 2000; McIntosh et al. 2004; Shiembob et al. 2006). In addition, specific members of the family bind to and influence the activities of GABAB GPCRs, K+ channels, and neuronal VGSCs (Robinson and Norton 2014).
This family belongs to the: Conotoxin Superfamily.
References associated with 8.B.32 family:
Alonso, D., Z. Khalil, N. Satkunanthan, and B.G. Livett. (2003). Drugs from the sea: conotoxins as drug leads for neuropathic pain and other neurological conditions. Mini Rev Med Chem 3: 785-787. 14529519
Cartier, G.E., D. Yoshikami, W.R. Gray, S. Luo, B.M. Olivera, and J.M. McIntosh. (1996). A new α-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors. J. Biol. Chem. 271: 7522-7528. 8631783
Guo, M., J. Yu, X. Zhu, D. Zhangsun, and S. Luo. (2021). Characterization of an α 4/7-Conotoxin LvIF from That Selectively Blocks α3β2 Nicotinic Acetylcholine Receptor. Mar Drugs 19:. 34356823
Kuryatov, A., F. Olale, J. Cooper, C. Choi, and J. Lindstrom. (2000). Human alpha6 AChR subtypes: subunit composition, assembly, and pharmacological responses. Neuropharmacology 39: 2570-2590. 11044728
Liu, Z., H. Li, N. Liu, C. Wu, J. Jiang, J. Yue, Y. Jing, and Q. Dai. (2012). Diversity and evolution of conotoxins in Conus virgo, Conus eburneus, Conus imperialis and Conus marmoreus from the South China Sea. Toxicon 60: 982-989. 22781954
Luo, S., D. Zhangsun, C.I. Schroeder, X. Zhu, Y. Hu, Y. Wu, M.M. Weltzin, S. Eberhard, Q. Kaas, D.J. Craik, J.M. McIntosh, and P. Whiteaker. (2014). A novel α4/7-conotoxin LvIA from Conus lividus that selectively blocks α3β2 vs. α6/α3β2β3 nicotinic acetylcholine receptors. FASEB J. 28: 1842-1853. 24398291
McIntosh, J.M., C. Dowell, M. Watkins, J.E. Garrett, D. Yoshikami, and B.M. Olivera. (2002). Alpha-conotoxin GIC from Conus geographus, a novel peptide antagonist of nicotinic acetylcholine receptors. J. Biol. Chem. 277: 33610-33615. 12114524
McIntosh, J.M., L. Azam, S. Staheli, C. Dowell, J.M. Lindstrom, A. Kuryatov, J.E. Garrett, M.J. Marks, and P. Whiteaker. (2004). Analogs of α-conotoxin MII are selective for alpha6-containing nicotinic acetylcholine receptors. Mol Pharmacol 65: 944-952. 15044624
Peng, C., S. Tang, C. Pi, J. Liu, F. Wang, L. Wang, W. Zhou, and A. Xu. (2006). Discovery of a novel class of conotoxin from Conus litteratus, lt14a, with a unique cysteine pattern. Peptides 27: 2174-2181. 16797781
Rashid, M.H., S. Mahdavi, and S. Kuyucak. (2013). Computational studies of marine toxins targeting ion channels. Mar Drugs 11: 848-869. 23528952
Robinson, S.D. and R.S. Norton. (2014). Conotoxin gene superfamilies. Mar Drugs 12: 6058-6101. 25522317
Shiembob, D.L., R.L. Roberts, C.W. Luetje, and J.M. McIntosh. (2006). Determinants of α-conotoxin BuIA selectivity on the nicotinic acetylcholine receptor beta subunit. Biochemistry 45: 11200-11207. 16964981
Teichert, R.W., E. López-Vera, J. Gulyas, M. Watkins, J. Rivier, and B.M. Olivera. (2006). Definition and characterization of the short alphaA-conotoxins: a single residue determines dissociation kinetics from the fetal muscle nicotinic acetylcholine receptor. Biochemistry 45: 1304-1312. 16430227
Teichert, R.W., R. Jacobsen, H. Terlau, D. Yoshikami, and B.M. Olivera. (2007). Discovery and characterization of the short kappaA-conotoxins: a novel subfamily of excitatory conotoxins. Toxicon 49: 318-328. 17118419
Turner, M., S. Eidemiller, B. Martin, A. Narver, J. Marshall, L. Zemp, K.A. Cornell, J.M. McIntosh, and O.M. McDougal. (2009). Structural basis for α-conotoxin potency and selectivity. Bioorg Med Chem 17: 5894-5899. 19628399