ArticleNature nanotechnology2024
Single-molecule sensing inside stereo- and regio-defined hetero-nanopores.
Article in Nature nanotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- A self-assembled peptide forms α-helical nanopores for ultrasensitive biomarker profiling.Nature nanotechnology · 2026Article
- Single-Molecule Fingerprinting of Unlabeled Full-Length Proteins Using an Aerolysin Nanopore.Journal of the American Chemical Society · 2026Article
- A universal deep learning framework for empowering nanopore identification by reinforcing temporal signals.Nature communications · 2026Article
- Bioinformatic and computational biophysics tools for nanopore engineering: a review from standard approaches to machine learning advancements.Journal of nanobiotechnology · 2026Review
- Nanopipette-DNA-Nanopore Hybrid System for Small Molecule Detection.ChemPlusChem · 2026Article
- Selective and Controllable Trapping of Single Proteins in Nanopores Using Reversible Covalent Bonds.ACS nano · 2026Article
- Understanding single-molecule reactions using nanopore-based techniques.Nature chemistry · 2025Review
- Redesign of Translocon EXP2 Nanopore for Detecting Peptide Fragments.Small methods · 2025Article
- Exploring the diffusion of DNA strands into nanoporous structures for establishing a universal electrochemical biosensor.Chemical science · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Heteromeric pore-forming proteins often contain recognition patterns or stereospecific selection filters. However, the construction of heteromeric pore-forming proteins for single-molecule sensing is challenging due to the uncontrollability of producing position isomers and difficulties in purification of regio-defined products. To overcome these preparation obstacles, we present an in situ strategy involving single-molecule chemical modification of a heptameric pore-forming protein to build a stereo- and regio-specific heteromeric nanopore (hetero-nanopore) with a subunit stoichiometric ratio of 3:4. The steric hindrance inherent in the homo-nanopore of K238C aerolysin directs the stereo- and regio-selective modification of maleimide derivatives. Our method utilizes real-time ionic current recording to facilitate controlled voltage manipulation for stoichiometric modification and position-based side-isomer removal. Single-molecule experiments and all-atom molecular dynamics simulations revealed that the hetero-nanopore features an asymmetric stereo- and regio-defined residue structure. The hetero-nanopore produced was characterized by mass spectrometry and single-particle cryogenic electron microscopy. In a proof-of-concept single-molecule sensing experiment, the hetero-nanopore exhibited 95% accuracy for label-free discrimination of four peptide stereoisomers with single-amino-acid structural and chiral differences in the mixtures. The customized hetero-nanopores could advance single-molecule sensing.
Indexed as
Identifiers
39164412What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.