7UUZ

Structure of the sodium/iodide symporter (NIS) in complex with perrhenate and sodium

7UUZ の概要

• エントリーDOI: 10.2210/pdb7uuz/pdb
• EMDBエントリー: 26807
• 分子名称: Sodium/iodide cotransporter, SODIUM ION, PERRHENATE, ... (4 entities in total)
• 機能のキーワード: nis, iodide, symporter, cryo-em, transport protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 74892.61

構造登録者

Ravera, S.,Nicola, J.P.,Salazar-De Simone, G.,Sigworth, F.,Karakas, E.,Amzel, L.M.,Bianchet, M.,Carrasco, N. (登録日: 2022-04-29, 公開日: 2022-12-21, 最終更新日: 2024-06-12)

主引用文献

Ravera, S.,Nicola, J.P.,Salazar-De Simone, G.,Sigworth, F.J.,Karakas, E.,Amzel, L.M.,Bianchet, M.A.,Carrasco, N.
Structural insights into the mechanism of the sodium/iodide symporter.
Nature, 612:795-801, 2022

PubMed Abstract: The sodium/iodide symporter (NIS) is the essential plasma membrane protein that mediates active iodide (I) transport into the thyroid gland, the first step in the biosynthesis of the thyroid hormones-the master regulators of intermediary metabolism. NIS couples the inward translocation of I against its electrochemical gradient to the inward transport of Na down its electrochemical gradient. For nearly 50 years before its molecular identification, NIS was the molecule at the centre of the single most effective internal radiation cancer therapy: radioiodide (I) treatment for thyroid cancer. Mutations in NIS cause congenital hypothyroidism, which must be treated immediately after birth to prevent stunted growth and cognitive deficiency. Here we report three structures of rat NIS, determined by single-particle cryo-electron microscopy: one with no substrates bound; one with two Na and one I bound; and one with one Na and the oxyanion perrhenate bound. Structural analyses, functional characterization and computational studies show the substrate-binding sites and key residues for transport activity. Our results yield insights into how NIS selects, couples and translocates anions-thereby establishing a framework for understanding NIS function-and how it transports different substrates with different stoichiometries and releases substrates from its substrate-binding cavity into the cytosol.

PubMed: 36517601
DOI: 10.1038/s41586-022-05530-2

実験手法

ELECTRON MICROSCOPY (3.2 Å)