Activating an invertebrate bistable opsin with the all- trans 6.11 retinal analog

• 成果类型: Article
• 署名作者: Rodrigues, Matthew J.; Tejero, Oliver; Muhle, Jonas; Pamula, Filip; Das, Ishita; Tsai, Ching - Ju; Terakita, Akihisa; Sheves, Mordechai; Schertler, Gebhard F. X.
• 署名单位: Swiss Federal Institutes of Technology Domain; Paul Scherrer Institute; Swiss Federal Institutes of Technology Domain; ETH Zurich; Weizmann Institute of Science; Osaka Metropolitan University; Osaka Metropolitan University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13453
• DOI: 10.1073/pnas.2406814121
• 发表日期: 2024-07-30
• 关键词: rhodopsin

摘要

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.