Kv channel gating requires a compatible S4-S5 linker and bottom part of S6, constrained by non-interacting residues.

Kv channel gating requires a compatible S4-S5 linker and bottom part of S6, constrained by non-interacting residues.
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DOI:
10.1085/jgp.200810048
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发表时间:
2008-12
期刊:
The Journal of general physiology
影响因子:
--
通讯作者:
Snyders DJ
Snyders DJ
中科院分区:
其他
文献类型:
--
作者:
Labro AJ;Raes AL;Grottesi A;Van Hoorick D;Sansom MS;Snyders DJ

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电压相关的 K+ 通道通过机电耦合将电压传感器运动转换为栅极打开或关闭。为了在功能上测试S4-S5接头(L45)和S6的细胞质末端(S6T)之间的相互作用是否构成这种偶联,hKv1.5中的L45被相应的hKv2.1序列替换。这种交换是不能容忍的,但可以通过交换 S6T 来挽救。交换 L45 和 S6T 将 hKv2.1 动力学转移到 hKv1.5 背景,同时保留电压依赖性。 hKv1.5中L45和S6T的一对一残基替换扫描进一步表明,S6T需要是α-螺旋并形成“缝隙”,其中存在L45的残基I422和T426。这些残基将机械能转移到 S6T 缝隙上,而 S6T 和 L45 中不参与相互作用的其他残基则维持正确的偶联结构。
Voltage-dependent K+ channels transfer the voltage sensor movement into gate opening or closure through an electromechanical coupling. To test functionally whether an interaction between the S4-S5 linker (L45) and the cytoplasmic end of S6 (S6T) constitutes this coupling, the L45 in hKv1.5 was replaced by corresponding hKv2.1 sequence. This exchange was not tolerated but could be rescued by also swapping S6T. Exchanging both L45 and S6T transferred hKv2.1 kinetics to an hKv1.5 background while preserving the voltage dependence. A one-by-one residue substitution scan of L45 and S6T in hKv1.5 further shows that S6T needs to be α-helical and forms a “crevice” in which residues I422 and T426 of L45 reside. These residues transfer the mechanical energy onto the S6T crevice, whereas other residues in S6T and L45 that are not involved in the interaction maintain the correct structure of the coupling.
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