Aflatoxin B1 (AFB1), produced by fungi of the genus Aspergillus, is the most toxic and carcinogenic mycotoxin among the classes of aflatoxins. Previous research showed that AFB1 affects vitamin D receptor (VDR) expression. In the present study, integrated computational and experimental studies were carried out to investigate how AFB1 can interfere with Vitamin D signalling. A competitive antagonism of AFB1 toward RXRα and VDR was hypothesized by comparing the docked complex of AFB1/RXRα and AFB1/VDR ligand-binding domain (LBD) with the X-ray structures of RXRα and VDR bound to known ligands. Accordingly, we demonstrated that AFB1 can affect vitamin D-mediated transcriptional activation of VDR by impairing the formation of protein complexes containing both VDR-RXRα and RXRα/RAR and affecting the subcellular localization of VDR and RXRα. As a whole, our data indicate that AFB1 can interfere with different molecular pathways triggered by vitamin D with an antagonistic mechanism of action.

黄曲霉毒素 B1 (AFB1) 由曲霉属真菌产生，是黄曲霉毒素中毒性最强、致癌性最强的霉菌毒素。先前的研究表明，AFB1 会影响维生素 D 受体 (VDR) 的表达。在本研究中，进行了综合计算和实验研究，以研究 AFB1 如何干扰维生素 D 信号传导。通过比较 AFB1/RXRα 和 AFB1/VDR 配体结合域 (LBD) 的对接复合物与与已知配体结合的 RXRα 和 VDR 的 X 射线结构，假设 AFB1 对 RXRα 和 VDR 具有竞争性拮抗作用。因此，我们证明AFB1可以通过损害含有VDR-RXRα和RXRα/RAR的蛋白质复合物的形成并影响VDR和RXRα的亚细胞定位来影响维生素D介导的VDR转录激活。总的来说，我们的数据表明 AFB1 可以通过拮抗作用机制干扰维生素 D 触发的不同分子途径。