• Orbit 16 TC

    fully parallel recording of 16 bilayers

2022 - Resolving Isomeric Posttranslational Modifications Using a Biological Nanopore as a Sensor of Molecular Shape

Icon Orbit  Orbit 16 (a predecessor model of the Orbit 16 TC instrument) publication in the Journal of the American Chemical Society (2022)

Authors:
Ensslen T., Sarthak K., Aksimentiev A., Behrends J.C.

Journal:
Journal of the American Chemical Society (2022) doi: 10.1021/jacs.2c06211


Abstract: 

The chemical nature and precise position of posttranslational modifications (PTMs) in proteins or peptides are crucial for various severe diseases, such as cancer. State-of-the-art PTM diagnosis is based on elaborate and costly mass-spectrometry or immunoassay-based approaches, which are limited in selectivity and specificity. Here, we demonstrate the use of a protein nanopore to differentiate peptides─derived from human histone H4 protein─of identical mass according to the positions of acetylated and methylated lysine residues. Unlike sequencing by stepwise threading, our method detects PTMs and their positions by sensing the shape of a fully entrapped peptide, thus eliminating the need for controlled translocation. Molecular dynamics simulations show that the sensitivity to molecular shape derives from a highly nonuniform electric field along the pore. This molecular shape-sensing principle offers a path to versatile, label-free, and high-throughput characterizations of protein isoforms.


Download here

Back to Overview

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.