Susankova Klara, Ettrich Rudiger, Vyklicky Ladislav, Teisinger Jan, Vlachova Viktorie
Department of Cellular Neurophysiology, Institute of Physiology, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic.
J Neurosci. 2007 Jul 11;27(28):7578-85. doi: 10.1523/JNEUROSCI.1956-07.2007.
The transient receptor potential vanilloid receptor-1 (TRPV1) is a sensory neuron-specific nonselective cation channel that is gated in response to various noxious stimuli: pungent vanilloids, low pH, noxious heat, and depolarizing voltages. By its analogy to K+ channels, the S6 inner helix domain of TRPV1 (Y666-G683) is a prime candidate to form the most constricted region of the permeation pathway and might therefore encompass an as-yet-unmapped gate of the channel. Using alanine-scanning mutagenesis, we identified 16 of 17 residues, that when mutated affected the functionality of the TRPV1 channel with respect to at least one stimulus modality. T670A was the only substitution producing the wild-type channel phenotype, whereas Y666A and N676A were nonfunctional but present at the plasma membrane. The periodicity of the functional effects of mutations within the TRPV1 inner pore region is consistent with an alpha-helical structure in which T670 and A680 might play the roles of two bending "hinges."
瞬时受体电位香草酸受体1（TRPV1）是一种感觉神经元特异性非选择性阳离子通道，可响应各种有害刺激而门控：辛辣香草酸、低pH值、有害热和去极化电压。通过与钾离子通道类比，TRPV1的S6内螺旋结构域（Y666 - G683）是形成通透途径最狭窄区域的主要候选者，因此可能包含该通道尚未确定位置的门控。利用丙氨酸扫描诱变，我们在17个残基中鉴定出16个，这些残基发生突变时，至少在一种刺激模式下会影响TRPV1通道的功能。T670A是唯一产生野生型通道表型的替换，而Y666A和N676A无功能，但存在于质膜上。TRPV1内孔区域内突变功能效应的周期性与一种α - 螺旋结构一致，其中T670和A680可能起到两个弯曲“铰链”的作用。
