Department of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
Nat Commun. 2022 May 2;13(1):2380. doi: 10.1038/s41467-022-30082-4.
Thyroid hormones are essential regulators of metabolism, development, and growth. They are formed from pairs of iodinated tyrosine residues within the precursor thyroglobulin (TG), a 660-kDa homodimer of the thyroid gland, by an oxidative coupling reaction. Tyrosine pairs that give rise to thyroid hormones have been assigned within the structure of human TG, but the process of hormone formation is poorly understood. Here we report a ~3.3-Å cryo-EM structure of native bovine TG with nascent thyroid hormone formed at one of the predicted hormonogenic sites. Local structural rearrangements provide insight into mechanisms underlying thyroid hormone formation and stabilization.
甲状腺激素是新陈代谢、发育和生长的重要调节剂。它们由甲状腺球蛋白（TG）前体中的成对碘化酪氨酸残基形成，甲状腺球蛋白（TG）是甲状腺的 660kDa 同源二聚体，通过氧化偶联反应形成。在人类 TG 的结构中已经分配了产生甲状腺激素的酪氨酸对，但激素形成的过程还不太清楚。在这里，我们报道了一个天然牛 TG 的约 3.3-Å 冷冻电镜结构，其中一个预测的激素生成位点上形成了新生甲状腺激素。局部结构重排为甲状腺激素形成和稳定的机制提供了深入了解。
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