Dubinsky W P, Mayorga-Wark O, Schultz S G
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1770-4. doi: 10.1073/pnas.89.5.1770.
A synthetic peptide composed of the first 22 amino acid residues of the Drosophila Shaker K+ channel inhibits a voltage-gated K+ channel in basolateral membrane vesicles from Necturus enterocytes reconstituted in planar phospholipid bilayers when added to the solution bathing the inner surface of this channel but not when added to the solution bathing its outer surface. A modified peptide in which the leucine in the 7 position is replaced with phenylalanine is also an effective inhibitor, but replacement of the leucine-7 with lysine or glutamate, or digestion with trypsin, renders the peptide ineffective; replacement of the leucine-7 with glycine markedly reduces but does not abolish the effectiveness of the peptide as an inhibitor. These results are analogous to those reported for the Shaker K+ channel +ADHoshi, T., Zagotta, W.N. & Aldrich, R.W. (1990) Science 250, 533-538; and Zagotta, W.N., Hoshi, T. & Aldrich, R.W. (1990) Science 250, 568-571.+BD and suggest that the molecular anatomy of the receptor at the inner face of the Necturus K+ channel with which the peptide interacts to bring about inhibition of that channel may be similar to that of the Shaker K+ channel.
由果蝇Shaker钾通道的前22个氨基酸残基组成的合成肽，当添加到浴于该通道内表面的溶液中时，会抑制在平面磷脂双层中重组的美西螈肠细胞基底外侧膜囊泡中的电压门控钾通道，但添加到浴于其外表面的溶液中时则不会。一种在第7位的亮氨酸被苯丙氨酸取代的修饰肽也是一种有效的抑制剂，但将第7位的亮氨酸替换为赖氨酸或谷氨酸，或用胰蛋白酶消化，会使该肽失去活性；将第7位的亮氨酸替换为甘氨酸会显著降低但不会消除该肽作为抑制剂的有效性。这些结果与报道的关于Shaker钾通道的结果相似 +ADHoshi, T., Zagotta, W.N. & Aldrich, R.W. (1990) Science 250, 533 - 538; and Zagotta, W.N., Hoshi, T. & Aldrich, R.W. (1990) Science 250, 568 - 571.+BD，并表明该肽与之相互作用以抑制美西螈钾通道的内表面受体的分子结构可能与Shaker钾通道的相似。
