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TitleCryo-EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States.
Journal, issue, pagesAngew Chem Int Ed Engl, Vol. 60, Issue 16, Page 8678-8682, Year 2021
Publish dateApr 12, 2021
AuthorsSabrina Pospich / Florian Küllmer / Veselin Nasufović / Johanna Funk / Alexander Belyy / Peter Bieling / Hans-Dieter Arndt / Stefan Raunser /
PubMed AbstractActin 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 ...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.
External linksAngew Chem Int Ed Engl / PubMed:33449370 / PubMed Central
MethodsEM (helical sym.) / EM (single particle)
Resolution2.9 - 3.6 Å
Structure data

11787

7ahn

EMDB-11787, PDB-7ahn:
Cryo-EM structure of F-actin stabilized by cis-optoJASP-8
Method: EM (helical sym.) / Resolution: 2.9 Å

11790

7ahq

EMDB-11790, PDB-7ahq:
Cryo-EM structure of F-actin stabilized by trans-optoJASP-8
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-PO4:
PHOSPHATE ION

ChemComp-RLZ:
~{N}-[4-[(4~{R},7~{R},10~{S},13~{S},15~{E},19~{S})-4-(4-hydroxyphenyl)-7-(1~{H}-indol-3-ylmethyl)-8,13,15,19-tetramethyl-2,6,9,12-tetrakis(oxidanylidene)-1-oxa-5,8,11-triazacyclononadec-15-en-10-yl]butyl]-~{N}'-[5-methoxy-2-[(~{Z})-(3,4,5-trimethoxyphenyl)diazenyl]phenyl]butanediamide

Source
  • oryctolagus cuniculus (rabbit)
KeywordsSTRUCTURAL PROTEIN / Cytoskeleton / jasplakinolide / azobenzene photoswitch / stabilized-actin filament

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