Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States

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 i...

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Autores principales: Pospich, Sabrina, Küllmer, Florian, Nasufović, Veselin, Funk, Johanna, Belyy, Alexander, Bieling, Peter, Arndt, Hans‐Dieter, Raunser, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048601/
https://www.ncbi.nlm.nih.gov/pubmed/33449370
http://dx.doi.org/10.1002/anie.202013193
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author Pospich, Sabrina
Küllmer, Florian
Nasufović, Veselin
Funk, Johanna
Belyy, Alexander
Bieling, Peter
Arndt, Hans‐Dieter
Raunser, Stefan
author_facet Pospich, Sabrina
Küllmer, Florian
Nasufović, Veselin
Funk, Johanna
Belyy, Alexander
Bieling, Peter
Arndt, Hans‐Dieter
Raunser, Stefan
author_sort Pospich, Sabrina
collection PubMed
description 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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spelling pubmed-80486012021-04-19 Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States Pospich, Sabrina Küllmer, Florian Nasufović, Veselin Funk, Johanna Belyy, Alexander Bieling, Peter Arndt, Hans‐Dieter Raunser, Stefan Angew Chem Int Ed Engl Communications 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. John Wiley and Sons Inc. 2021-03-04 2021-04-12 /pmc/articles/PMC8048601/ /pubmed/33449370 http://dx.doi.org/10.1002/anie.202013193 Text en © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Communications
Pospich, Sabrina
Küllmer, Florian
Nasufović, Veselin
Funk, Johanna
Belyy, Alexander
Bieling, Peter
Arndt, Hans‐Dieter
Raunser, Stefan
Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States
title Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States
title_full Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States
title_fullStr Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States
title_full_unstemmed Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States
title_short Cryo‐EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States
title_sort cryo‐em resolves molecular recognition of an optojasp photoswitch bound to actin filaments in both switch states
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048601/
https://www.ncbi.nlm.nih.gov/pubmed/33449370
http://dx.doi.org/10.1002/anie.202013193
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