The gate of the influenza virus M2 proton channel is formed by a single tryptophan residue
The gate of the influenza virus M2 proton channel is formed by a single tryptophan residue
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DOI：
10.1074/jbc.m206582200
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发表时间：
2002-10-18
影响因子：
4.8
通讯作者：
Pinto, LH
中科院分区：
文献类型：
--
作者：
Tang, YJ;Zaitseva, F;Pinto, LH
已知流感病毒M - 2质子选择性离子通道在内涵体腔中病毒脱壳期间使病毒粒子内部酸化过程中至关重要。M - 2蛋白是一种同型四聚体，包含四个19个氨基酸残基的跨膜（TM）结构域。这些TM结构域具有多种功能，因为它们包含通道孔并且还将蛋白锚定在膜上。M - 2蛋白受pH调控，因此我们测量了pH门控电流、通道孔对Cu²⁺的可及性以及一种蛋白质修饰试剂对一系列TM结构域突变的M - 2蛋白的影响。结果表明，M - 2离子通道的门控由TM结构域第41位残基的单个侧链控制，并且这种特性由一个吲哚部分介导。与许多离子通道（其门由蛋白质的整个片段形成）不同，我们的数据表明M - 2离子通道蛋白具有一种极其简单的模型，当外部pH值高时，色氨酸（41）的侧链堵塞M - 2通道的孔，而当外部pH值低时，该侧链离开孔。因此，色氨酸（41）侧链充当打开和关闭孔的门。
The influenza virus M-2 proton-selective ion channel is known to be essential for acidifying the interior of virions during virus uncoating in the lumen of endosomes. The M-2 protein is a homotetramer that contains four 19-residue transmembrane (TM) domains. These TM domains are multifunctional, because they contain the channel pore and also anchor the protein in membranes. The M-2 protein is gated by pH, and thus we have measured pH-gated currents, the accessibility of the pore to Cu2+, and the effect of a protein-modifying reagent for a series of TM domain mutant M-2 proteins. The results indicate that gating of the M-2 ion channel is governed by a single side chain at residue 41 of the TM domain and that this property is mediated by an indole moiety. Unlike many ion channels where the gate is formed by a whole segment of a protein, our data suggest a model of striking simplicity for the M-2 ion channel protein, with the side chain of Trp(41) blocking the pore of the M-2 channel when pH(out) is high and with this side chain leaving the pore when pH(out) is low. Thus, the Trp(41) side chain acts as the gate that opens and closes the pore.