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De novo design of semisynthetic protein nanopores

Schnaider, L.; Hatstat, A. K.; Scott, A. J.; Tan, S. K.; Hambley, R. G.; Dawson, W. M.; Griffiths, R. C.; Kormos, R. C.; Melo, A. A.; Tse, E.; Polizzi, N. C.; Wallace, E. J.; Merz, G. E.; DeGrado, W. F.

2025-09-08 biochemistry
10.1101/2025.09.08.674823 bioRxiv
Show abstract

Protein nanopores are essential components of single-molecule oligonucleotide sequencing and sensing devices. Here, we demonstrate that installing additional de novo subunits enables large-scale architectural changes of nanopore complexes. We design de novo proteins that integrate seamlessly with the CsgG pore to form 18-subunit, 315-kilodalton complexes with precisely sculpted pore architectures and tailored ion conduction, opening new possibilities for engineering enhanced nanopores with customized structural and functional properties.

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