Gating of the TrkH ion channel by its associated RCK protein TrkA.

Gating of the TrkH ion channel by its associated RCK protein TrkA.
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DOI:
10.1038/nature12056
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发表时间:
2013-04-18
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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TrkH属于K+转运蛋白的超家族,其是细菌在低外部K+浓度下生长所需的。来自副溶血性弧菌的TrkH的晶体结构表明,TrkH类似于K+通道,并且可能具有与K+通道显著不同的门控机制。TrkH与TrkA组装,TrkA是一种包含两个调节K+电导或RCK结构域的胞质蛋白,其存在于某些K+通道中并控制其门控。然而,关于TrkH是否是离子通道以及它如何被TrkA调节的基本问题仍然没有解决。在这里,我们显示了TrkH的单通道活性,其通过TrkA被ATP上调。我们报告了四聚体TrkA环的两种结构,一种与TrkH复合,另一种是孤立的,其中该环呈现两种截然不同的构象。这些结果表明ATP如何通过诱导TrkA的构象变化来增加TrkH活性的机制。
TrkH belongs to a superfamily of K+ transport proteins required for growth of bacteria in low external K+ concentrations. The crystal structure of TrkH from Vibrio parahaemolyticus showed that TrkH resembles a K+ channel, and may have a gating mechanism substantially different from K+ channels. TrkH assembles with TrkA, a cytosolic protein comprising two Regulate-the-Conductance-of-K+, or RCK domains, which are found in certain K+ channels and control their gating. However, fundamental questions on whether TrkH is an ion channel and how it is regulated by TrkA remain unresolved. Here we show single-channel activity of TrkH that is upregulated by ATP via TrkA. We report two structures of the tetrameric TrkA ring, one in complex with TrkH and one in isolation, in which the ring assumes two dramatically different conformations. These results suggest a mechanism for how ATP increases TrkH activity by inducing conformational changes in TrkA.
DOI: 10.1126/science.280.5360.69
发表时间: 1998-04-03
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发表时间: 2010-02
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影响因子: --
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