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首页> 外文期刊>Nature >NIP domain prevents N-type inactivation in voltage-gated potassium channels.
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NIP domain prevents N-type inactivation in voltage-gated potassium channels.

机译：NIP域可防止电压门控钾通道中的N型失活。

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摘要

Shaker-related voltage-gated K+ (Kv) channels are assembled from ion-conducting K(v)alpha subunits, which are integral membrane proteins, and auxiliary K(v)beta subunits. This leads to the formation of highly diverse heteromultimeric Kv channels that mediate outward currents with a wide range of time courses for inactivation. Two principal inactivation mechanisms have been recognized: C-type inactivation correlated with carboxy-terminal K(v)alpha-subunit structures, and N-type inactivation conferred by 'ball' domains in the amino termini of certain K(v)alpha and K(v)beta subunits. Assembly of heteromultimers with one or more K(v)alpha- and/or K(v)beta ball domains appears to be an essential principle of the generation of A-type Kv channel diversity. Here we show that, unexpectedly, the presence of K(v)alpha- or K(v)beta-ball domains does not dominate the gating phenotype in heteromultimers containing Kv1.6alpha subunits. These heteromultimers mediate non-inactivating currents because of the dominant-negative activity of a new type of N-type inactivation-prevention (NIP) domain present in the Kv1.6 amino terminus. Mutations in the NIP domain lead to loss of function, and its transfer to another K(v)alpha subunit leads to gain of function. Our discovery of the NIP domain, which neutralizes the activity of K(v)alpha- and K(v)beta-inactivation gates, establishes a new determinant for the gating behaviour of heteromultimeric Kv channels.
机译：摇床相关的电压门控K +（Kv）通道是由离子传导性K（v）alpha亚基和辅助K（v）beta亚基组装而成的。这导致形成高度多样化的异源多聚体Kv通道，该通道介导具有广泛灭活时间范围的外向电流。已经认识到两种主要的失活机制：与羧基端K（v）alpha-亚基结构相关的C型失活，以及某些K（v）alpha和K的氨基末端中“球”结构域赋予的N型失活（v）β亚基。具有一个或多个K（v）α-和/或K（v）β球形结构域的异源多聚体的组装似乎是A型Kv通道多样性产生的基本原理。在这里，我们表明，出乎意料的是，在包含Kv1.6alpha亚基的异源多聚体中，K（v）α-或K（v）β-球结构域的存在并不主导门控表型。这些异源多聚体介导非灭活电流，因为存在于Kv1.6氨基末端的新型N型灭活（NIP）预防域的显性负活性。 NIP域中的突变会导致功能丧失，将其转移到另一个K（v）alpha亚基会导致功能增强。我们发现的NIP结构域可中和K（v）alpha-和K（v）beta失活门的活性，为异多聚体Kv通道的门控行为建立了新的决定因素。

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