Heginbotham L, Lu Z, Abramson T, MacKinnon R
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115.
Biophys J. 1994 Apr;66(4):1061-7. doi: 10.1016/S0006-3495(94)80887-2.
Potassium channels share a highly conserved stretch of eight amino acids, a K+ channel signature sequence. The conserved sequence falls within the previously defined P-region of voltage-activated K+ channels. In this study we investigate the effect of mutations in the signature sequence of the Shaker channel on K+ selectivity determined under bi-ionic conditions. Nonconservative substitutions of two threonine residues and the tyrosine residue leave selectivity intact. In contrast, mutations at some positions render the channel nonselective among monovalent cations. These findings are consistent with a proposal that the signature sequence contributes to a selectivity filter. Furthermore, the results illustrate that the hydroxyl groups at the third and fourth positions, and the aromatic group at position seven, are not essential in determining K+ selectivity.
钾通道共有一段由八个氨基酸组成的高度保守序列，即钾离子通道特征序列。该保守序列位于先前定义的电压激活钾通道的P区域内。在本研究中，我们研究了Shaker通道特征序列中的突变对在双离子条件下测定的钾离子选择性的影响。两个苏氨酸残基和酪氨酸残基的非保守取代使选择性保持不变。相比之下，某些位置的突变使通道在单价阳离子之间不具有选择性。这些发现与特征序列有助于形成选择性过滤器的提议一致。此外，结果表明，第三和第四位置的羟基以及第七位置的芳香基团在决定钾离子选择性方面并非必不可少。
