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Unique Electrical Signature of Phosphate for Specific Single-Molecule Detection of Peptide Phosphorylation

Single-molecule measurements of biomaterials bring novel insights into cellular events. For almost all of these events, post-translational modifications (PTMs), which alter the properties of proteins through their chemical modifications, constitute essential regulatory mechanisms. However, suitable...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2022-09, Vol.144 (38), p.17449-17456
Main Authors: Harashima, Takanori, Egami, Yoshiyuki, Homma, Kanji, Jono, Yuki, Kaneko, Satoshi, Fujii, Shintaro, Ono, Tomoya, Nishino, Tomoaki
Format: Article
Language:English
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Summary:Single-molecule measurements of biomaterials bring novel insights into cellular events. For almost all of these events, post-translational modifications (PTMs), which alter the properties of proteins through their chemical modifications, constitute essential regulatory mechanisms. However, suitable single-molecule methodology to study PTMs is very limited. Here we show single-molecule detection of peptide phosphorylation, an archetypal PTM, based on electrical measurements. We found that the phosphate group stably bridges a nanogap between metal electrodes and exhibited high electrical conductance, which enables specific single-molecule detection of peptide phosphorylation. The present methodology paves the way to single-molecule studies of PTMs, such as single-molecule kinetics for enzymatic modification of proteins as shown here.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.2c05787