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

FEBS Letters

Seagar, Michael J.²  Takahashi, Masami³  Kim, Jae Il¹  Raymond, Cecile²  Sasaki, Toru³  Minami, Kazushi³  Sato, Kazuki³  Martin-Moutot, Nicole²  Van Renterghem, Catherine²  Ohtake, Atsuko³ 

[1] Kwangju Institute of Life Science and Technology, Kwangsan-ku, Kwangju 506-712, South Korea;INSERM U374, Institut Jean Roche, Faculté de Médecine Secteur Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France;Mitsubishi Kasei Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan

关键词: ω-Conotoxin MVIIC;    Calcium channel;    Ala-scanning;    Fmoc;    9-fluorenylmethoxycarbonyl;    GSH;    reduced glutathione;    GSSG;    oxidized glutathione;    GVIA;    ω-conotoxin GVIA;    HPLC;    high performance liquid chromatography;    [125I]GVIA;    [125I]ω-conotoxin GVIA;    [125I]MVIIC;    [125I][Nle12]ω-conotoxin MVIIC;    MALDI-TOF-MS;    matrix assisted laser desorption/ionization time-of-flight mass spectrometry;    MVIIA;    ω-conotoxin MVIIA;    MVIIC;    ω-conotoxin MVIIC;    ODS;    octadecylsilane;    TFA;    trifluoroacetic acid;    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;    K2A indicates an analog in which Lys2 is replaced with Ala;   

DOI  :  10.1016/S0014-5793(00)01263-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

ω-Conotoxin MVIIC binds to P/Q-type calcium channels with high affinity and N-type channels with low affinity. To reveal the residues essential for subtype selectivity, we synthesized Ala-scanning analogs of MVIIC. Binding assays using rat cerebellar P₂ membranes suggested that Thr¹¹, Tyr¹³ and Lys² are essential for binding to both N- and P/Q-type channels, whereas Lys⁴ and Arg²² are important for binding to P/Q-type channels. These results suggest that MVIIC interacts with P/Q-type channels via a large surface, in good agreement with previous observations using chimeric analogs.

【 授权许可】

Unknown