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  4. In Vitro-Evolved Peptides Bind Monomeric Actin and Mimic Actin-Binding Protein Thymosin-β4
 
research article

In Vitro-Evolved Peptides Bind Monomeric Actin and Mimic Actin-Binding Protein Thymosin-β4

Gübeli, Raphael J.  
•
Bertoldo, Davide  
•
Shimada, Kenji
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May 21, 2021
ACS Chemical Biology

Actin is the most abundant protein in eukaryotic cells and is key to many cellular functions. The filamentous form of actin (F-actin) can be studied with help of natural products that specifically recognize it, as for example fluorophore-labeled probes of the bicyclic peptide phalloidin, but no synthetic probes exist for the monomeric form of actin (G-actin). Herein, we have panned a phage display library consisting of more than 10 billion bicyclic peptides against G-actin and isolated binders with low nanomolar affinity and greater than 1000-fold selectivity over F-actin. Sequence analysis revealed a strong similarity to a region of thymosin-β4, a protein that weakly binds G-actin, and competition binding experiments confirmed a common binding region at the cleft between actin subdomains 1 and 3. Together with F-actin-specific peptides that we also isolated, we evaluated the G-actin peptides as probes in pull-down, imaging, and competition binding experiments. While the F-actin peptides were applied successfully for capturing actin in cell lysates and for imaging, the G-actin peptides did not bind in the cellular context, most likely due to competition with thymosin-β4 or related endogenous proteins for the same binding site.

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Type
research article
DOI
10.1021/acschembio.0c00825
Web of Science ID

WOS:000656055500006

Author(s)
Gübeli, Raphael J.  
Bertoldo, Davide  
Shimada, Kenji
Gerhold, Christian B.
Hurst, Verena
Takahashi, Yuichiro
Harada, Kai
Mothukuri, Ganesh K.  
Wilbs, Jonas  
Harata, Masahiko
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Date Issued

2021-05-21

Published in
ACS Chemical Biology
Volume

16

Issue

5

Start page

820

End page

828

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LPPT  
FunderGrant Number

FNS

141945

Other foundations

HFSP

Available on Infoscience
November 21, 2021
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/179850
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