MUTATIONS IN THE K+ CHANNEL SIGNATURE SEQUENCE

MUTATIONS IN THE K+ CHANNEL SIGNATURE SEQUENCE
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DOI:
10.1016/s0006-3495(94)80887-2
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发表时间:
1994-04-01
影响因子:
3.4
通讯作者:
MACKINNON, R
MACKINNON, R
中科院分区:
生物学3区
文献类型:
--
作者:
HEGINBOTHAM, L;LU, Z;MACKINNON, R

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钾离子通道共有一段高度保守的8个氨基酸,这是一个钾离子通道特征序列。保守序列福尔斯位于先前定义的电压激活K+通道的P区。在这项研究中,我们调查的影响突变的签名序列的振荡器通道上的K+的选择性确定在双离子条件下。两个苏氨酸残基和酪氨酸残基的非保守取代保持选择性不变。相反,在某些位置的突变使得通道在一价阳离子之间是非选择性的。这些发现与签名序列有助于选择性过滤器的建议是一致的。此外,结果表明,在第三和第四位的羟基基团,和在位置7的芳香族基团,在确定K+选择性不是必不可少的。
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.