A CLUSTER OF HYDROPHOBIC AMINO-ACID-RESIDUES REQUIRED FOR FAST NA+-CHANNEL INACTIVATION
A CLUSTER OF HYDROPHOBIC AMINO-ACID-RESIDUES REQUIRED FOR FAST NA+-CHANNEL INACTIVATION
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DOI：
10.1073/pnas.89.22.10910
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发表时间：
1992-11-15
影响因子：
11.1
通讯作者：
CATTERALL, WA
中科院分区：
文献类型：
--
作者：
WEST, JW;PATTON, DE;CATTERALL, WA
神经动作电位的内向Na+电流因失活而终止。先前的报道表明，结构域III和IV之间的细胞内接头内的缺失消除了失活，但保守的碱性和成对的酸性氨基酸的突变几乎没有影响。在这里，我们表明，取代谷氨酰胺的三个成簇的疏水氨基酸，Ile-1488，苯丙氨酸-1489，和Met-1490，完全消除快速失活。Met-1490单独取代显著减缓失活，Ile-1488单独取代既减缓失活又使其不完全，Phe-1489单独取代几乎完全消除失活。这些结果证明了Phe-1489在Na+通道失活中的重要作用。有人提出，Ile-1488，Phe-1489和Met-1490的疏水簇作为一个疏水锁，稳定的Na+通道失活的铰链盖机制中的失活状态。
The inward Na+ current underlying the action potential in nerve is terminated by inactivation. The preceding report shows that deletions within the intracellular linker between domains III and IV remove inactivation, but mutation of conserved basic and paired acidic amino acids has little effect. Here we show that substitution of glutamine for three clustered hydrophobic amino acids, Ile-1488, Phe-1489, and Met-1490, completely removes fast inactivation. Substitution of Met-1490 alone slows inactivation significantly, substitution of Ile-1488 alone both slows inactivation and makes it incomplete, and substitution of Phe-1489 alone removes inactivation nearly completely. These results demonstrate an essential role of Phe-1489 in Na+-channel inactivation. It is proposed that the hydrophobic cluster of Ile-1488, Phe-1489, and Met-1490 serves as a hydrophobic latch that stabilizes the inactivated state in a hinged-lid mechanism of Na+-channel inactivation.