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Mapping Full Conformational Transition Dynamics of Intrinsically Disordered Proteins Using a Single-Molecule Nanocircuit.
Yin, Dongbao; Xiong, Ruoyao; Yang, Zhiheng; Feng, Jianfei; Liu, Wenzhe; Li, Shiyun; Li, Mingyao; Ruan, Hao; Li, Jie; Li, Lidong; Lai, Luhua; Guo, Xuefeng.
Afiliación
  • Yin D; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Xiong R; State Key Laboratory for Advanced Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Haidian District, Beijing 100083, P. R. China.
  • Yang Z; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Feng J; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Liu W; State Key Laboratory for Advanced Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Haidian District, Beijing 100083, P. R. China.
  • Li S; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Li M; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Ruan H; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Li J; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Li L; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Lai L; Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, 292 Chengfu Road, Haidian District, Beijing 100871, P. R. China.
  • Guo X; State Key Laboratory for Advanced Metals and Materials, School of Materials Science and Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Haidian District, Beijing 100083, P. R. China.
ACS Nano ; 2024 Sep 14.
Article en En | MEDLINE | ID: mdl-39276130
ABSTRACT
Intrinsically disordered proteins (IDPs) are emerging therapeutic targets for human diseases. However, probing their transient conformations remains challenging because of conformational heterogeneity. To address this problem, we developed a biosensor using a point-functionalized silicon nanowire (SiNW) that allows for real-time sampling of single-molecule dynamics. A single IDP, N-terminal transactivation domain of tumor suppressor protein p53 (p53TAD1), was covalently conjugated to the SiNW through chemical engineering, and its conformational transition dynamics was characterized as current fluctuations. Furthermore, when a globular protein ligand in solution bound to the targeted p53TAD1, protein-protein interactions could be unambiguously distinguished from large-amplitude current signals. These proof-of-concept experiments enable semiquantitative, realistic characterization of the structural properties of IDPs and constitute the basis for developing a valuable tool for protein profiling and drug discovery in the future.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Nano Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Nano Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos