Role of Thr11 in the binding of ω‐conotoxin MVIIC to N‐type Ca2+ channels

FEBS Letters

Seagar, Michael J.¹  Takahashi, Masami³  Raymond, Cecile¹  Minami, Kazushi³  Sato, Kazuki³  Martin-Moutot, Nicole¹  Van Renterghem, Catherine¹  Ohtake, Atsuko³  Mori, Yasuo² 

[1] INSERM U464, Institut Jean Roche, Faculté de Médecine Secteur Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France;Department of Information Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan;Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan

关键词: ω-Conotoxin MVIIC;    Ca2+ channel;    Binding assay;    Patch-clamp;    Abu;    aminobutyric acid;    BHK;    baby hamster kidney;    GVIA;    ω-conotoxin GVIA;    [125I]GVIA;    [125I]ω-conotoxin GVIA;    [125I]MVIIC;    [125I]ω-conotoxin MVIIC;    MVIIA;    ω-conotoxin MVIIA;    MVIIC;    ω-conotoxin MVIIC;    Analogs are designated by a letter and number indicating the identity and position of the substituted amino acid;    followed by a letter indicating the identity of the replacement residue. For example;    T11L indicates an analog in which Thr11 is replaced with Leu;   

DOI  :  10.1016/S0014-5793(01)02183-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

As replacement of Thr¹¹ 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 P₂ 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 Ca²⁺ channels. Inhibition of Ba²⁺ current by the analogs did not completely correlate with binding affinity, although binding to BHK cells was comparable to rat cerebellar membranes.

【 授权许可】

Unknown