Animal vision depends on opsins, a category of G protein-coupled receptor (GPCR) that achieves light sensitivity by covalent attachment to retinal. Typically binding as an inverse agonist, 11-cis retinal photoisomerizes to the all-trans isomer and activates the receptor, initiating downstream signaling cascades. Retinal bound to bistable opsins isomerizes back to the 11-cis state after absorption of a second photon, inactivating the receptor. Bistable opsins are essential for invertebrate vision and nonvisual light perception across the animal kingdom. While crystal structures are available for bistable opsins in the inactive state, it has proven difficult to form homogeneous populations of activated bistable opsins either via illumination or reconstitution with all-trans retinal. Here, we show that a nonnatural retinal analog, all-trans retinal 6.11 (ATR6.11), can be reconstituted with the invertebrate bistable opsin, Jumping Spider Rhodopsin-1 (JSR1). Biochemical activity assays demonstrate that ATR6.11 functions as a JSR1 agonist. ATR6.11 binding also enables complex formation between JSR1 and signaling partners. Our findings demonstrate the utility of retinal analogs for biophysical characterization of bistable opsins, which will deepen our understanding of light perception in animals.

中文翻译：

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用全反式 6.11 视网膜类似物激活无脊椎动物双稳态视蛋白


动物视觉依赖于视蛋白，视蛋白是一类 G 蛋白偶联受体 (GPCR)，通过与视网膜共价附着来实现光敏感性。 11-顺式视网膜通常作为反向激动剂结合，光异构化为全反式异构体并激活受体，启动下游信号级联。与双稳态视蛋白结合的视黄醛在吸收第二个光子后异构化回 11-顺式状态，从而使受体失活。双稳态视蛋白对于整个动物界的无脊椎动物视觉和非视觉光感知至关重要。虽然晶体结构可用于非活性状态的双稳态视蛋白，但事实证明，通过照明或用全反式视网膜重构来形成均匀的活化双稳态视蛋白群体是困难的。在这里，我们展示了一种非天然视网膜类似物，全反式视网膜 6.11 (ATR6.11)，可以用无脊椎动物双稳态视蛋白跳蛛视紫红质-1 (JSR1) 重建。生化活性测定表明 ATR6.11 具有 JSR1 激动剂的功能。 ATR6.11 结合还使得 JSR1 和信号传导伙伴之间能够形成复合物。我们的研究结果证明了视网膜类似物在双稳态视蛋白生物物理表征中的实用性，这将加深我们对动物光感知的理解。