한빛사논문
- 조회473
Ki-Baek Jeong1,2,8, Minju Ryu1,3,8, Jin-Sik Kim1,2,8, Minsoo Kim4, Jejoong Yoo4, Minji Chung1, Sohee Oh1, Gyunghee Jo5, Seong-Gyu Lee5, Ho Min Kim5,6, Mi-Kyung Lee1,2,3 & Seung-Wook Chi1,3,7
1Disease Target Structure Research Center, Division of Biomedical Research, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
2Critical Diseases Diagnostics Convergence Research Center, KRIBB, Daejeon 34141, Republic of Korea.
3Department of Proteome Structural Biology, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34113, Republic of Korea.
4Department of Physics, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea.
5Center for Biomolecular and Cellular Structure, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea.
6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.
7School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea.
8These authors contributed equally: Ki-Baek Jeong, Minju Ryu, Jin-Sik Kim.
Corresponding authors : Correspondence to Mi-Kyung Lee or Seung-Wook Chi.
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.
논문정보
- Research article
- 2023년 04월 (BRIC 등록일 2023-04-07)
- 국내 연구진
- 생명과학 > 구조생물 및 생물물리학
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