当前位置: X-MOL 学术Nat. Struct. Mol. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Allosteric regulation of mammalian Na+/I- symporter activity by perchlorate.
Nature Structural & Molecular Biology ( IF 16.8 ) Pub Date : 2020-05-25 , DOI: 10.1038/s41594-020-0417-5
Alejandro Llorente-Esteban 1, 2, 2 , Rían W Manville 3 , Andrea Reyna-Neyra 1, 2, 2 , Geoffrey W Abbott 3 , L Mario Amzel 4 , Nancy Carrasco 1, 2, 2
Affiliation  

The Na+/I symporter (NIS), the plasma membrane protein that actively transports I (stoichiometry 2Na+:1I) in thyroid physiology and radioiodide-based thyroid cancer treatment, also transports the environmental pollutant perchlorate (stoichiometry 1Na+:1ClO4), which competes with I for transport. Until now, the mechanism by which NIS transports different anion substrates with different stoichiometries has remained unelucidated. We carried out transport measurements and analyzed these using a statistical thermodynamics–based equation and electrophysiological experiments to show that the different stoichiometry of ClO4 transport is due to ClO4 binding to a high-affinity non-transport allosteric site that prevents Na+ from binding to one of its two sites. Furthermore, low concentrations of ClO4 inhibit I transport not only by competition but also, critically, by changing the stoichiometry of I transport to 1:1, which greatly reduces the driving force. The data reveal that ClO4 pollution in drinking water is more dangerous than previously thought.



中文翻译:

高氯酸盐对哺乳动物 Na+/I- 同向转运体活性的变构调节。

Na + /I 同向转运蛋白 (NIS),一种在甲状腺生理学和基于放射性碘的甲状腺癌治疗中主动转运 I (化学计量 2Na + :1I )的质膜蛋白,也转运环境污染物高氯酸盐(化学计量 1Na + : 1ClO 4 − ), 与 I 竞争运输。到目前为止,NIS 传输具有不同化学计量的不同阴离子底物的机制仍未阐明。我们进行了传输测量,并使用基于统计热力学的方程和电生理学实验对这些进行了分析,以表明 ClO 4 传输的不同化学计量是由于 ClO 4 与高亲和力非传输变构位点结合,从而阻止 Na +从绑定到它的两个站点之一。此外,低浓度的 ClO 4 不仅通过竞争抑制 I −运输,而且重要的是,还通过改变 I −的化学计量来抑制 I − 运输。传输到1:1,大大降低了驱动力。数据显示,饮用水中的ClO 4 −污染比之前认为的更危险。

更新日期:2020-05-25
down
wechat
bug