Herding cats: Label-based approaches in protein translocation through nanopore sensors for single-molecule protein sequence analysis

iScience. 2021 Aug 25;24(9):103032. doi: 10.1016/j.isci.2021.103032. eCollection 2021 Sep 24.


Proteins carry out life's essential functions. Comprehensive proteome analysis technologies are thus required for a full understanding of the operating principles of biological systems. While current proteomics techniques suffer from limitations in sensitivity and/or throughput, nanopore technology has the potential to enable de novo protein identification through single-molecule sequencing. However, a significant barrier to achieving this goal is controlling protein/peptide translocation through the nanopore sensor for processive strand analysis. Here, we review recent approaches that use a range of techniques, from oligonucleotide conjugation to molecular motors, aimed at driving protein strands and peptides through protein nanopores. We further discuss site-specific protein conjugation chemistry that could be combined with these translocation approaches as future directions to achieve single-molecule protein detection and sequencing of native proteins.

Keywords: Biochemistry; Bioorganic chemistry; Proteomics.

Publication types

  • Review