Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227, Dortmund, Germany.
Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich-Schiller-University, Humboldtstr. 10, 07743, Jena, Germany.
Angew Chem Int Ed Engl. 2021 Apr 12;60(16):8678-8682. doi: 10.1002/anie.202013193. Epub 2021 Mar 4.
Actin is essential for key processes in all eukaryotic cells. Cellpermeable optojasps provide spatiotemporal control of the actin cytoskeleton, confining toxicity and potentially rendering F-actin druggable by photopharmacology. Here, we report cryo electron microscopy (cryo-EM) structures of both isomeric states of one optojasp bound to actin filaments. The high-resolution structures reveal for the first time the pronounced effects of photoswitching a functionalized azobenzene. By characterizing the optojasp binding site and identifying conformational changes within F-actin that depend on the optojasp isomeric state, we refine determinants for the design of functional F-actin photoswitches.
肌动蛋白对于所有真核细胞的关键过程都是必不可少的。细胞通透性的光学钳提供了对肌动蛋白细胞骨架的时空控制,限制了毒性,并通过光药理学使 F-肌动蛋白具有潜在的可用药性。在这里,我们报告了一个光夹与肌动蛋白丝结合的两种异构体状态的低温电子显微镜(cryo-EM)结构。这些高分辨率结构首次揭示了功能化偶氮苯光开关的显著影响。通过对光夹结合位点进行表征,并确定依赖于光夹异构体状态的 F-肌动蛋白构象变化,我们改进了设计功能性 F-肌动蛋白光开关的决定因素。