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BP: Fachverband Biologische Physik

BP 15: Protein Structure and Single Molecules

BP 15.4: Hauptvortrag

Mittwoch, 7. September 2022, 11:00–11:30, H13

The importance of water in membrane receptor function — •Anthony Watts — Biochemistry Department, South Parks Road, Oxford, OX1 3QU, UK

Resolving conformational changes in membrane receptors in response to a stimulus, and capturing their functionally relevant dynamics, is very challenging. Over the years we have addressed this challenge using a range of spectroscopic approaches1,2,3 on functionally competent photoreceptors, often in their natural membranes4 or Lipodisqs*5. We have complemented this work with functional studies, mass spec characterization6 and very high resolution (1.07Å) crystallography7,8, as well as photo-induced x-ray, free electron laser studies (XFELS), without the use of detergents and including natural lipids. This high-resolution information reveals waters and their importance in both receptor activation-desensitization and QM(SCC-DFTB)/MM MD trajectories give information about the activation process. The system studied is achearhodopsin-3 (AR3), a photoreceptor utilized widely in optogenetics despite the lack of structures. The arrangement of internal water networks is responsible for the faster photocycle compared to homologs. These insights have generic implications for other receptors. (1). Higman et al., (2011) Angew. Chemie 50(36):8432 (2). Dijkman et al., (2018) Nature Comms. 9:1710 (3). Dijkman et al., (2020) Science Advances, 6:33 (4). Lavington & Watts (2020) Biophys. Rev. 12:1287 (5). Juarez et al., (2019) Chem. Phys. Lipids 221:167 (6). Hoi et al., (2021) Nano Letters, 21(7):2824 (7). Axford et al., (2022) Acta Cryst D78:52 (8). Juarez et al (2021) Nature Comms. 12:629