National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01-114250
米国
引用
ジャーナル: Nature / 年: 2022 タイトル: Structural insights into the mechanism of the sodium/iodide symporter. 著者: Silvia Ravera / Juan Pablo Nicola / Glicella Salazar-De Simone / Fred J Sigworth / Erkan Karakas / L Mario Amzel / Mario A Bianchet / Nancy Carrasco / 要旨: 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 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.
想定した対称性 - 点群: C1 (非対称) / アルゴリズム: FOURIER SPACE / 解像度のタイプ: BY AUTHOR / 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: cryoSPARC 詳細: Particles were symmetry expanded and local refinement was performed on one of the two protomers. 使用した粒子像数: 205030
初期 角度割当
タイプ: MAXIMUM LIKELIHOOD
最終 角度割当
タイプ: MAXIMUM LIKELIHOOD
FSC曲線 (解像度の算出)
-
原子モデル構築 1
精密化
空間: REAL / プロトコル: FLEXIBLE FIT
得られたモデル
PDB-7uuy: Structure of the sodium/iodide symporter (NIS)