The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel

被引:169
作者
Minor, DL [1 ]
Lin, YF
Mobley, BC
Avelar, A
Jan, YN
Jan, LY
Berger, JM
机构
[1] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA
[4] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0092-8674(00)00088-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Kv voltage-gated potassium channels share a cytoplasmic assembly domain, T1. Recent mutagenesis of two T1 C-terminal loop residues implicates T1 in channel gating. However, structural alterations of these mutants leave open the question concerning direct involvement of T1 in gating. We find in mammalian Kv1.2 that gating depends critically on residues at complementary T1 surfaces in an unusually polar interface. An isosteric mutation in this interface causes surprisingly little structural alteration while stabilizing the dosed channel and increasing the stability of T1 tetramers. Replacing T1 with a tetrameric coiled-coil destabilizes the closed channel. Together, these data suggest that structural changes involving the buried polar T1 surfaces play a key role in the conformational changes leading to channel opening.
引用
收藏
页码:657 / 670
页数:14
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