Binding of Ala-scanning analogs of omega-conotoxin MVIIC to N- and P/Q-type calcium channels

omega-Conotoxin MVIIC binds to P/Q-type calcium channels with high affinity and N-type channels with low affinity. To reveal the residues essential fo r subtype selectivity, we synthesized Ala-scanning analogs of MVIIC. Bindin g assays using rat cerebellar P-2 membranes suggested that Thr(11), Tyr(13) and Lys(2) are essential for binding to both N- and P/Q-type channels, whe reas Lys(4) and Arg(22) are important for binding to P/Q-type channels. The se results suggest that MVIIC interacts with P/Q-type channels via a large surface, in good agreement with previous observations using chimeric analog s. (C) 2000 Federation of European Biochemical Societies.