Resolving Isomeric Posttranslational Modifications Using a Biological Nanopore as a Sensor of Molecular Shape.
J Am Chem Soc
; 144(35): 16060-16068, 2022 09 07.
Article
en En
| MEDLINE
| ID: mdl-36007197
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 peptidesâderived from human histone H4 proteinâof 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Nanoporos
Límite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania