Details

Autor(en) / Beteiligte

• Jeong, Ki-Baek
• Ryu, Minju
• Kim, Jin-Sik
• Kim, Minsoo
• Yoo, Jejoong
• Chung, Minji
• Oh, Sohee
• Jo, Gyunghee
• Lee, Seong-Gyu
• Kim, Ho Min
• Lee, Mi-Kyung
• Chi, Seung-Wook

Titel

Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore

Ist Teil von

• Nature communications, 2023-04, Vol.14 (1), p.1461-1461, Article 1461

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• In drug discovery, efficient screening of protein-drug interactions (PDIs) is hampered by the limitations of current biophysical approaches. Here, we develop a biological nanopore sensor for single-molecule detection of proteins and PDIs using the pore-forming toxin YaxAB. Using this YaxAB nanopore, we demonstrate label-free, single-molecule detection of interactions between the anticancer Bcl-xL protein and small-molecule drugs as well as the Bak-BH3 peptide. The long funnel-shaped structure and nanofluidic characteristics of the YaxAB nanopore enable the electro-osmotic trapping of diverse folded proteins and high-resolution monitoring of PDIs. Distinctive nanopore event distributions observed in the two-dimensional (ΔI/I -versus-I ) plot illustrate the ability of the YaxAB nanopore to discriminate individual small-molecule drugs bound to Bcl-xL from non-binders. Taken together, our results present the YaxAB nanopore as a robust platform for label-free, ultrasensitive, single-molecule detection of PDIs, opening up a possibility for low-cost, highly efficient drug discovery against diverse drug targets.