Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor and regulate various physiological responses. Photoactivated CRYs undergo oligomerization, which increases the binding affinity to downstream signaling partners. Despite decades of research on the activation of CRYs, little is known about how they are inactivated. Binding of blue-light inhibitors of cryptochromes (BICs) to CRY2 suppresses its photoactivation, but the underlying mechanism remains unknown. Here, we report crystal structures of CRY2N (CRY2 PHR domain) and the BIC2-CRY2N complex with resolutions of 2.7 and 2.5 Å, respectively. In the BIC2-CRY2N complex, BIC2 exhibits an extremely extended structure that sinuously winds around CRY2N. In this way, BIC2 not only restrains the transfer of electrons and protons from CRY2 to FAD during photoreduction but also interacts with the CRY2 oligomer to return it to the monomer form. Uncovering the mechanism of CRY2 inactivation lays a solid foundation for the investigation of cryptochrome protein function.

中文翻译：

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BIC介导的拟南芥隐色素2失活的结构见解。

隐色染料（CRYs）是植物中的蓝光受体，其将FAD用作辅助因子并调节各种生理反应。光活化的CRY经历低聚，这增加了对下游信号传导伴侣的结合亲和力。尽管对CRY的活化进行了数十年的研究，但对CRY的失活知之甚少。隐色染料（BIC）的蓝光抑制剂与CRY2的结合会抑制其光活化，但其潜在机制仍不清楚。在这里，我们报道了CRY2N（CRY2 PHR域）和BIC2-CRY2N配合物的晶体结构，其分辨率分别为2.7和2.5Å。在BIC2-CRY2N络合物中，BIC2表现出极度延伸的结构，蜿蜒地缠绕在CRY2N周围。通过这种方式，BIC2不仅抑制了光还原过程中电子和质子从CRY2到FAD的转移，而且还与CRY2低聚物相互作用，使其返回单体形式。揭示CRY2失活的机制为研究隐色蛋白功能奠定了坚实的基础。