Molecular determinants of permeation in a fluoride-specific ion channel.
Molecular determinants of permeation in a fluoride-specific ion channel.
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DOI：
10.7554/elife.31259
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发表时间：
2017-09-27
期刊：
影响因子：
7.7
通讯作者：
Miller C
中科院分区：
文献类型：
--
作者：
Last NB;Sun S;Pham MC;Miller C
Fluc家族的氟离子通道对抗由环境F-积累引起的毒性。虽然晶体结构是已知的，但密集堆积的孔区域已经排除了离子路径的描绘。在这里，我们绘制了Fluc孔和表征其运输的化学要求。氢键供体残基的阶梯产生区分离子传导途径的“极性轨道”。令人惊讶的是，虽然轨道极性是保守的，但极性在几个位置上是功能性的。位于孔一端的苏氨酸通过其β-分支甲基参与重要的相互作用。通过四极离子相互作用直接协调F-的两个关键的中心苯丙氨酸不能被芳香族、非极性或极性侧链功能性取代。唯一的功能性替代是甲硫氨酸，其通过其部分正的γ-亚甲基模拟苯丙氨酸的四极相互作用来配位F-。这些结果表明，选择性运输强氢键F-阴离子的不寻常的化学要求。
Fluoride ion channels of the Fluc family combat toxicity arising from accumulation of environmental F-. Although crystal structures are known, the densely packed pore region has precluded delineation of the ion pathway. Here we chart out the Fluc pore and characterize its chemical requirements for transport. A ladder of H-bond donating residues creates a ‘polar track’ demarking the ion-conduction pathway. Surprisingly, while track polarity is well conserved, polarity is nonetheless functionally dispensable at several positions. A threonine at one end of the pore engages in vital interactions through its β-branched methyl group. Two critical central phenylalanines that directly coordinate F- through a quadrupolar-ion interaction cannot be functionally substituted by aromatic, non-polar, or polar sidechains. The only functional replacement is methionine, which coordinates F- through its partially positive γ-methylene in mimicry of phenylalanine’s quadrupolar interaction. These results demonstrate the unusual chemical requirements for selectively transporting the strongly H-bonding F- anion.