Enantioselective protein-sterol interactions mediate regulation of both prokaryotic and eukaryotic inward rectifier K+ channels by cholesterol.
Enantioselective protein-sterol interactions mediate regulation of both prokaryotic and eukaryotic inward rectifier K+ channels by cholesterol.
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DOI：
10.1371/journal.pone.0019393
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Nichols CG
中科院分区：
文献类型：
--
作者：
D'Avanzo N;Hyrc K;Enkvetchakul D;Covey DF;Nichols CG
胆固醇是所有哺乳动物细胞质膜的主要固醇组分，并且在细胞功能和生长中起关键作用。以前的研究表明，胆固醇抑制内向整流K+（Kir）通道，但没有区分这是否是由于直接蛋白质-甾醇相互作用或间接的脂质双层的物理性质的变化。使用纯化的细菌和真核细胞Kir通道重建到具有受控脂质组成的脂质体中，我们通过86 Rb+内流测定证明细菌Kir通道（KirBac1.1和KirBac3.1）和人Kir2.1都受到胆固醇的抑制，最有可能是通过将通道锁定到长期关闭状态，而对映体ent-胆固醇不会抑制这些通道。这些数据表明，胆固醇调节Kir通道通过直接的蛋白质-固醇相互作用可能利用进化保守的结合口袋。
Cholesterol is the major sterol component of all mammalian cell plasma membranes and plays a critical role in cell function and growth. Previous studies have shown that cholesterol inhibits inward rectifier K+ (Kir) channels, but have not distinguished whether this is due directly to protein-sterol interactions or indirectly to changes in the physical properties of the lipid bilayer. Using purified bacterial and eukaryotic Kir channels reconstituted into liposomes of controlled lipid composition, we demonstrate by 86Rb+ influx assays that bacterial Kir channels (KirBac1.1 and KirBac3.1) and human Kir2.1 are all inhibited by cholesterol, most likely by locking the channels into prolonged closed states, whereas the enantiomer, ent-cholesterol, does not inhibit these channels. These data indicate that cholesterol regulates Kir channels through direct protein-sterol interactions likely taking advantage of an evolutionarily conserved binding pocket.
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