埃博毒素中第30位的甘氨酸是其对大电导钙激活钾通道与电压门控钾通道特异性的关键决定因素。

Glycine 30 in iberiotoxin is a critical determinant of its specificity for maxi-K versus K(V) channels.

作者信息

Schroeder Nathan, Mullmann Theodore J, Schmalhofer W A, Gao Ying-Duo, Garcia Maria L, Giangiacomo Kathleen M

机构信息

Department of Biochemistry, Temple University School of Medicine, 3420 N. Broad Street, Philadelphia, PA 19140, USA.

出版信息

FEBS Lett. 2002 Sep 11;527(1-3):298-302. doi: 10.1016/s0014-5793(02)03256-8.

DOI:10.1016/s0014-5793(02)03256-8

PMID:12220678

Abstract

Iberiotoxin (IbTX) is a remarkably selective alpha-K toxin peptide (alpha-KTx) inhibitor of the maxi-K channel. In contrast, the highly homologous charybdotoxin inhibits both the maxi-K and K(V)1.3 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(V)1.3 channels were monitored through dose-dependent displacement of specifically bound iodinated alpha-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.

摘要

伊比利亚毒素（IbTX）是一种对大电导钙激活钾通道具有显著选择性的α-钾毒素肽（α-KTx）抑制剂。相比之下，高度同源的蝎毒素以相似的高亲和力同时抑制大电导钙激活钾通道和K(V)1.3通道。本研究通过对IbTX进行诱变来探究这种特异性的分子基础。通过监测突变肽与表达这些通道的细胞膜上特异性结合的碘化α-KTx肽的剂量依赖性置换，来研究突变肽与大电导钙激活钾通道和K(V)1.3通道的相互作用。这些研究结果表明，IbTX第30位存在甘氨酸是其特异性的主要决定因素，而IbTX中四个独特酸性残基的存在并非如此。