Premium
Role of Thr 11 in the binding of ω‐conotoxin MVIIC to N‐type Ca 2+ channels
Author(s) -
Minami Kazushi,
Raymond Cecile,
Martin-Moutot Nicole,
Ohtake Atsuko,
Van Renterghem Catherine,
Takahashi Masami,
Seagar Michael J.,
Mori Yasuo,
Sato Kazuki
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02183-4
Subject(s) - chemistry , conotoxin , amino acid , binding site , stereochemistry , membrane , voltage dependent calcium channel , calcium , biophysics , biochemistry , peptide , biology , organic chemistry
As replacement of Thr 11 of ω‐conotoxin MVIIC with Ala significantly reduced the affinity for both N‐ and P/Q‐type calcium channels, we examined the effect of substitution at this position with other residues. Binding assays using rat cerebellar P 2 membranes showed that the affinity is in the order of Leu>Val, aminobutyric acid, Thr>Asn≫Ser, Ala, Asp, Phe, Tyr for N‐type channels and Thr>Leu, Val, aminobutyric acid, Asn, Ser>Ala≫Asp, Phe, Tyr for P/Q‐type channels, suggesting that aliphatic amino acids with longer side chains are favorable for block of N‐type channels. The effects of substitution were examined electrophysiologically in BHK cells expressing N‐type Ca 2+ channels. Inhibition of Ba 2+ current by the analogs did not completely correlate with binding affinity, although binding to BHK cells was comparable to rat cerebellar membranes.