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Small Molecule Channels Harness Membrane Potential to Concentrate Potassium in trk1Δtrk2Δ Yeast.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-05-19 , DOI: 10.1021/acschembio.0c00180
Jennifer Hou 1 , Page N Daniels 1 , Martin D Burke 1, 2, 3, 4, 5
Affiliation  

Many protein ion channels harness membrane potential to move ions in opposition to their chemical gradient. Deficiencies of such proteins cause several human diseases, including cystic fibrosis, Bartter Syndrome, and proximal renal tubular acidosis. Using yeast as a eukaryotic model system, we asked whether, in the context of a protein ion channel deficiency in vivo, small molecule channels could similarly harness membrane potential to concentrate ions. Trk potassium transporters use membrane potential to move potassium from a relatively low concentration outside cells (∼15 mM) to one of >10× higher inside (150–500 mM); trk1Δtrk2Δ are unable to concentrate potassium or grow in standard media. Here we show that potassium-permeable, but not potassium-selective, small-molecule ion channels formed by amphotericin B can harness membrane potential to concentrate potassium and thereby restore trk1Δtrk2Δ growth. This finding expands the list of potential human channelopathies that might be addressed by a molecular prosthetics approach.

中文翻译:

小分子引导线束膜势富集trk1Δtrk2Δ酵母中的钾。

许多蛋白质离子通道利用膜电位来移动与其化学梯度相反的离子。此类蛋白质的缺乏会导致多种人类疾病,包括囊性纤维化,巴特综合征和近端肾小管酸中毒。我们使用酵母作为真核模型系统,询问是否在体内蛋白质离子通道缺乏的情况下,小分子通道可以类似地利用膜电位来浓缩离子。Trk钾转运蛋白利用膜电位将钾从相对低浓度的细胞外部(约15 mM)移动到高于10倍的内部(150-500 mM)中。trk1Δtrk2Δ无法浓缩钾或在标准培养基中生长。在这里,我们显示了由两性霉素B形成的钾可渗透而不是钾选择性的小分子离子通道,可以利用膜电位来浓缩钾,从而恢复trk1Δtrk2Δ的生长。这一发现扩大了可能通过分子修复方法解决的潜在人类通道病的清单。
更新日期:2020-06-19
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