Structural highlights
Function
CAS2_CONST Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them (PubMed:1390774). This toxin potently inhibits the rodent muscle nAChR (IC(50)=120 nM (adult subtype, alpha-1-beta-1-delta-epsilon/CHRNA1-CHRNB1-CHRND-CHRNE) and IC(50)=370 nM (fetal subtype, alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND)) and weakly inhibits neuronal nAChRs (PubMed:35357806). In contrast to alpha-conotoxins bearing 2 disulfide bonds (framework I), this conotoxin acts via a unique binding mode with the helix and the N- and C-termini buried in the binding pocket of muscle nAChRs (PubMed:35357806).[1] [2]
References
- ↑ Ramilo CA, Zafaralla GC, Nadasdi L, Hammerland LG, Yoshikami D, Gray WR, Kristipati R, Ramachandran J, Miljanich G, Olivera BM, et al.. Novel alpha Biochemistry. 1992 Oct 20;31(41):9919-26. PMID:1390774 doi:10.1021/bi00156a009
- ↑ 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
