State Key Laboratory of Surface Physics, Department of Physics, Fudan University, 200433, Shanghai, China.
Beijing Computational Science Research Center, 100193, Beijing, China.
Commun Biol. 2022 Oct 18;5(1):1103. doi: 10.1038/s42003-022-04054-9.
Cryptochromes are blue light receptors that mediate circadian rhythm and magnetic sensing in various organisms. A typical cryptochrome consists of a conserved photolyase homology region domain and a varying carboxyl-terminal extension across species. The structure of the flexible carboxyl-terminal extension and how carboxyl-terminal extension participates in cryptochrome's signaling function remain mostly unknown. In this study, we uncover the potential missing link between carboxyl-terminal extension conformational changes and downstream signaling functions. Specifically, we discover that the blue-light induced opening of carboxyl-terminal extension in C. reinhardtii animal-like cryptochrome can structurally facilitate its interaction with Rhythm Of Chloroplast 15, a circadian-clock-related protein. Our finding is made possible by two technical advances. Using single-molecule Förster resonance energy transfer technique, we directly observe the displacement of carboxyl-terminal extension by about 15 Å upon blue light excitation. Combining structure prediction and solution X-ray scattering methods, we propose plausible structures of full-length cryptochrome under dark and lit conditions. The structures provide molecular basis for light active conformational changes of cryptochrome and downstream regulatory functions.
隐花色素是一种蓝光受体，在各种生物中介导昼夜节律和磁感觉。典型的隐花色素由保守的光解酶同源区结构域和跨物种的变化羧基末端延伸组成。柔性羧基末端延伸的结构以及羧基末端延伸如何参与隐花色素的信号转导功能在很大程度上仍然未知。在这项研究中，我们揭示了羧基末端延伸构象变化与下游信号转导功能之间潜在的缺失联系。具体来说，我们发现蓝光照诱导的 C. reinhardtii 动物样隐花色素羧基末端延伸的开放可以在结构上促进其与节律相关蛋白 15 的相互作用。我们的发现得益于两项技术进步。使用单分子Förster 共振能量转移技术，我们直接观察到蓝光照激发时羧基末端延伸约 15 Å 的位移。结合结构预测和溶液 X 射线散射方法，我们提出了黑暗和光照条件下全长隐花色素的合理结构。这些结构为隐花色素的光活性构象变化和下游调节功能提供了分子基础。
