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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural conservation of ion conduction pathways in K channels and glutamate receptors.
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Structural conservation of ion conduction pathways in K channels and glutamate receptors.

机译：钾通道和谷氨酸受体中离子传导途径的结构保守性。

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摘要

Single channel recordings demonstrate that ion channels switch stochastically between an open and a closed pore conformation. In search of a structural explanation for this universal open/close behavior, we have uncovered a striking degree of amino acid homology across the pore-forming regions of voltage-gated K channels and glutamate receptors. This suggested that the pores of these otherwise unrelated classes of channels could be structurally conserved. Strong experimental evidence supports a hairpin structure for the pore-forming region of K channels. Consequently, we hypothesized the existence of a similar structure for the pore of glutamate receptors. In ligand-gated channels, the pore is formed by M2, the second of four putative transmembrane segments. A hairpin structure for M2 would affect the subsequent membrane topology, inverting the proposed orientation of the next segments, M3. We have tested this idea for the NR1 subunit of the N-methyl-D-aspartate receptor. Mutations that affected the glycosylation pattern of the NR1 subunit localize both extremes of the M3-M4 linker to the extracellular space. Whole cell currents and apparent agonist affinities were not affected by these mutations. Therefore it can be assumed that they represent the native transmembrane topology. The extracellular assignment of the M3-M4 linker challenged the current topology model by inverting M3. Taken together, the amino acid homology and the new topology suggest that the pore-forming M2 segment of glutamate receptors does not transverse the membrane but, rather, forms a hairpin structure, similar to that found in K channels.
机译：单通道记录表明离子通道在开放和封闭的孔构象之间随机切换。在寻找这种普遍的打开/关闭行为的结构解释时，我们发现了跨电压门控K通道和谷氨酸受体的成孔区域的氨基酸同源性惊人。这表明这些在其他方面不相关的通道的孔可以在结构上保守。有力的实验证据支持K通道孔形成区域的发夹结构。因此，我们假设谷氨酸受体的孔存在类似的结构。在配体门控通道中，孔是由M2形成的，M2是四个假定的跨膜片段中的第二个。 M2的发夹结构会影响后续的膜拓扑，从而颠倒下一个片段M3的拟议方向。我们已经针对N-甲基-D-天冬氨酸受体的NR1亚基测试了这个想法。影响NR1亚基糖基化模式的突变将M3-M4接头的两个极端都定位到细胞外空间。全细胞电流和表观激动剂亲和力不受这些突变的影响。因此，可以假定它们代表了天然的跨膜拓扑。 M3-M4接头的胞外分配通过反转M3挑战了当前的拓扑模型。总的来说，氨基酸同源性和新的拓扑结构表明，谷氨酸受体的成孔M2节段不横穿膜，而是形成发夹结构，类似于在K通道中发现的发夹结构。

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