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首页> 外文期刊>The FASEB Journal >Asn441 plays a key role in folding and function of the Na+/I? symporter (NIS)
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Asn441 plays a key role in folding and function of the Na+/I? symporter (NIS)

机译：ASN441在NA + / I的折叠和功能中起关键作用？ Symporter（NIS）

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The Na+/I? symporter (NIS) is a plasma membrane glycoprotein that mediates active I? transport in the thyroid, the first step in the biosynthesis of the iodine-containing thyroid hormones T3 and T4. Several NIS mutants have been identified as a cause of congenital I? transport defect (ITD), and their investigation has yielded valuable mechanistic information on NIS. Here we report a thorough characterization of the ITD-causing NIS mutation in which the sixth intracellular loop residues 439–443 are missing. This mutant protein was intracellularly retained, incompletely glycosylated, and intrinsically inactive. Engineering 5 Ala at positions 439–443 partially recovered cell surface targeting and activity (～15%). Strikingly, NIS with the sequence 439-AANAA-443, in which Asn was restored at position 441, was targeted to the plasma membrane and exhibited ～95% the transport activity of WT NIS. Based on our NIS homology model, we propose that the side chain of N441, a residue conserved throughout most of the SLC5 family, interacts with the main chain amino group of G444, capping the α-helix of transmembrane segment XII and thus stabilizing the structure of the molecule. Our data provide insight into a critical interhelical interaction required for NIS folding and activity.—Li, W., Nicola, J. P., Amzel, L. M., Carrasco, N. Asn441 plays a key role in folding and function of the Na+/I? symporter (NIS).
机译：na + / i？ Symporter（NIS）是一种蛋白质膜糖蛋白，介导活性I？在甲状腺中运输，含碘甲状腺激素T3和T4的生物合成的第一步。几个NIS突变体已被确定为先天性I的原因？运输缺陷（ITD），他们的调查在NIS上产生了有价值的机制信息。在这里，我们报告了彻底表征ITD导致的NIS突变，其中缺少第六个细胞内环残留物439-443。该突变蛋白是细胞内保留的，不完全的糖基化和本质上无活性。在位置439-443的工程5 Ala部分回收的细胞表面靶向和活性（〜15％）。引人注目的是，NIS与序列439-a anaa-443，其中ASN在位置441处恢复，靶向质膜，并显示出〜95％的WT NIs的运输活性。基于我们的NIS同源模型，我们提出了N441的侧链，在整个SLC5家族中保存的残留物，与G444的主链氨基相互作用，覆盖跨膜段XII的α-螺旋，从而稳定结构分子。我们的数据能够深入了解NIS折叠和活动所需的临界互生相互作用。-LI，W.，Nicola，J.P.，Amzel，L. M.，Carrasco，N.Asn441在Na + / I的折叠和功能中起着关键作用？ Symporter（NIS）。

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