Baudry N, Lejeune P J, Niccoli P, Vinet L, Carayon P, Mallet B
Unité 38 INSERM, Faculté de Médecine, Marseille, France.
FEBS Lett. 1996 Nov 4;396(2-3):223-6. doi: 10.1016/0014-5793(96)01107-6.
Formation of dityrosine bridges is a ubiquitous process mainly attributed to oxidative stress leading to protein degradation and cellular damages. Here we show that dityrosine formation is involved in a physiological process, thyroid hormone synthesis, and is strictly dependent on structural characteristics, namely N-glycans, presented by the protein acting as the prothyroid hormone. We used two isoforms of the N-terminal thyroid hormone forming domain (NTD) of human thyroglobulin: one without N-glycan (19 kDa isoform) and the other with high mannose type structures (25 kDa isoform). Both isoforms were able to form iodotyrosines after in vitro iodination. However, iodotyrosine coupling to form thyroxine did not occur with the unglycosylated 19 kDa NTD. In contrast, the 25 kDa isoform formed thyroxine. Strikingly, thyroxine synthesis was accompanied by dimerization of the 25 kDa isoform and formation of a dityrosine bridge; none of this was observed with the 19 kDa isoform. Taken as a whole, our results indicate that dimerization through dityrosine bridging accompanies and could have a role in thyroid hormone synthesis.
二酪氨酸桥的形成是一个普遍存在的过程，主要归因于氧化应激，氧化应激会导致蛋白质降解和细胞损伤。在此我们表明，二酪氨酸的形成参与了一个生理过程——甲状腺激素合成，并且严格依赖于作为促甲状腺激素的蛋白质所呈现的结构特征，即N -聚糖。我们使用了人甲状腺球蛋白N端甲状腺激素形成结构域（NTD）的两种同工型：一种没有N -聚糖（19 kDa同工型），另一种具有高甘露糖型结构（25 kDa同工型）。两种同工型在体外碘化后都能够形成碘酪氨酸。然而，未糖基化的19 kDa NTD不能发生碘酪氨酸偶联形成甲状腺素。相反，25 kDa同工型形成了甲状腺素。令人惊讶的是，甲状腺素合成伴随着25 kDa同工型的二聚化和二酪氨酸桥的形成；而19 kDa同工型未观察到这些现象。总体而言，我们的结果表明，通过二酪氨酸桥连的二聚化伴随着甲状腺激素合成，并且可能在其中发挥作用。
