Amino acid residues in transmembrane segment IX of the Na+/I- symporter play a role in its Na+ dependence and are critical for transport activity
Amino acid residues in transmembrane segment IX of the Na+/I- symporter play a role in its Na+ dependence and are critical for transport activity
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DOI：
10.1074/jbc.m700147200
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发表时间：
2007-08-31
影响因子：
4.8
通讯作者：
Carrasco, Nancy
中科院分区：
文献类型：
--
作者：
De la Vieja, Antonio;Reed, Mia D.;Carrasco, Nancy
Na+/I-同向转运体（NIS）是介导甲状腺、哺乳期乳腺和其他组织中Na+依赖性主动I-转运的关键质膜糖蛋白。NIS的跨膜段（TMS）IX中354位侧链的OH基团已被证明是NIS功能所必需的，如通过对导致先天性I-转运缺陷的T354 P NIS突变的研究所揭示的。TMS IX具有NIS中任何TMS中最多的含β-OH基团的氨基酸（Ser和Thr）。我们已经彻底地表征了NIS中TMS IX中所有Ser和Thr的功能意义，以及在SLC 5A蛋白家族的其他转运蛋白中高度保守的TMSIX中的其他残基的功能意义。在这里，我们表明，五个β-OH基团的残基（Thr-351，Ser-353，Thr-354，Ser-356，和Thr-357）和Asn-360，所有这些puridically面对的TMS IX中的螺旋的同一侧，加上Asp-369，位于膜/胞质溶胶界面，在NIS功能中发挥关键作用，似乎参与Na+结合/易位。
The Na+/I- symporter (NIS) is a key plasma membrane glycoprotein that mediates Na+-dependent active I- transport in the thyroid, lactating breast, and other tissues. The OH group of the side chain at position 354 in transmembrane segment (TMS) IX of NIS has been demonstrated to be essential for NIS function, as revealed by the study of the congenital I- transport defect-causing T354P NIS mutation. TMS IX has the most beta-OH group-containing amino acids (Ser and Thr) of any TMS in NIS. We have thoroughly characterized the functional significance of all Ser and Thr in TMS IX in NIS, as well as of other residues in TMSIX that are highly conserved in other transporters of the SLC5A protein family. Here we show that five beta-OH group-containing residues (Thr-351, Ser-353, Thr-354, Ser-356, and Thr-357) and Asn-360, all of which putatively face the same side of the helix in TMS IX, plus Asp-369, located in the membrane/cytosol interface, play key roles in NIS function and seem to be involved in Na+ binding/translocation.