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Gyunghee, Jo
단백질 커뮤니케이션 그룹
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Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore

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Title
Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore
Author(s)
Jeong, Ki-Baek; Ryu, Minju; Kim, Jin-Sik; Kim, Minsoo; Yoo, Jejoong; Chung, Minji; Oh, Sohee; Gyunghee Jo; Seong-Gyu Lee; Ho Min Kim; Lee, Mi-Kyung; Chi, Seung-Wook
Publication Date
2023-04
Journal
Nature Communications, v.14, no.1
Publisher
Nature Research
Abstract
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/Io-versus-IN) 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. © 2023, The Author(s).
URI
https://pr.ibs.re.kr/handle/8788114/13318
DOI
10.1038/s41467-023-37098-4
ISSN
2041-1723
Appears in Collections:
Pioneer Research Center for Biomolecular and Cellular Structure(바이오분자 및 세포구조 연구단) > Protein Communication Group(단백질 커뮤니케이션 그룹) > 1. Journal Papers (저널논문)
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