Glycine 30 in iberiotoxin is a critical determinant of its specificity for maxi‐K versus KV channels

FEBS Letters

Mullmann, Theodore J¹  Gao, Ying-Duo³  Giangiacomo, Kathleen M¹  Garcia, Maria L²  Schmalhofer, W.A²  Schroeder, Nathan¹ 

[1] Department of Biochemistry, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA;Department of Membrane Biochemistry and Biophysics, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA;Molecular Systems, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA

关键词: Iberiotoxin;    Maxi-K channel;    KV1.3 channel;    α-K peptide;    Charybdotoxin;    α-KTx;    α-K peptide;    ChTX or α-KTx 1.1;    charybdotoxin;    HgTX-1 or α-KTx 2.3;    hongotoxin-1;    IbTX or α-KTx 1.3;    iberiotoxin;    [125I]HgTX-1-A19Y/Y37F;    mono-iodinated HgTX-1-A19Y/Y37F;    [125I]IbTX-D19Y/Y36F;    mono-iodinated IbTX-D19Y/Y36F;    NxTX or α-KTx 2.1;    noxiustoxin;    K i;    toxin inhibition constant;   

DOI  :  10.1016/S0014-5793(02)03256-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Iberiotoxin (IbTX) is a remarkably selective α-K toxin peptide (α-KTx) inhibitor of the maxi-K channel. In contrast, the highly homologous charybdotoxin inhibits both the maxi-K and K_V1.3 channels with similar high affinity. The present study investigates the molecular basis for this specificity through mutagenesis of IbTX. The interactions of mutated peptides with maxi-K and K_V1.3 channels were monitored through dose-dependent displacement of specifically bound iodinated α-KTx peptides from membranes expressing these channels. Results of these studies suggest that the presence of a glycine at position 30 in IbTX is a major determinant of its specificity while the presence of four unique acidic residues in IbTX is not.

【 授权许可】

Unknown