Department of Biochemistry, University of Bayreuth, Universitätsstr. 30, 95447 Bayreuth, Germany.
Institut für Biochemie und Molekularbiologie, Universitätsklinikum Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53115 Bonn, Germany.
Biomolecules. 2024 Oct 28;14(11):1373. doi: 10.3390/biom14111373.
Iodothyronine deiodinases (Dio) are selenocysteine-containing membrane enzymes that activate and inactivate the thyroid hormones (TH) through reductive iodide eliminations. The three deiodinase isoforms are homodimers sharing highly conserved amino acid sequences, but they differ in their regioselectivities for the deiodination reaction and regulatory features. We have now solved a crystal structure of the mouse deiodinase 2 (Dio2) catalytic domain. It reveals a high overall similarity to the deiodinase 3 structure, supporting the proposed common mechanism, but also Dio2-specific features, likely mediating its unique properties. Activity studies with an artificially enforced Dio dimer further confirm that dimerization is required for activity and requires both the catalytic core and the enzyme's N-terminus. Cross-linking studies reveal the catalytic core's dimerization interface, providing insights into the architecture of the complete, active Dio homodimer.
碘甲状腺原氨酸脱碘酶（Dio）是含硒半胱氨酸的膜酶，通过还原碘消除作用激活和失活甲状腺激素（TH）。三种脱碘酶同工型都是同源二聚体，具有高度保守的氨基酸序列，但它们在脱碘反应的区域选择性和调节特征上有所不同。我们现在已经解决了小鼠脱碘酶 2（Dio2）催化结构域的晶体结构。它与脱碘酶 3 的结构高度相似，支持了提出的共同机制，但也有 Dio2 特异性特征，可能介导其独特的性质。用人工强制 Dio 二聚体进行的活性研究进一步证实，二聚化对于活性是必需的，并且需要催化核心和酶的 N 端。交联研究揭示了催化核心的二聚化界面，为完整、活性 Dio 同源二聚体的结构提供了见解。
