Cryo-EM resolves molecular recognition of an optojasp photoswitch bound to actin filaments in both switch states

Pospich S, Küllmer F, Nasufovic V, Funk J, Belyy A, Bieling P, Arndt HD, Raunser S. (2021) Angew Chem Int Ed Engl 


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.

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