Visualizing single-molecule conformational transition and binding dynamics of intrinsically disordered proteins.
Nat Commun
; 14(1): 5203, 2023 08 25.
Article
em En
| MEDLINE
| ID: mdl-37626077
ABSTRACT
Intrinsically disordered proteins (IDPs) play crucial roles in cellular processes and hold promise as drug targets. However, the dynamic nature of IDPs remains poorly understood. Here, we construct a single-molecule electrical nanocircuit based on silicon nanowire field-effect transistors (SiNW-FETs) and functionalize it with an individual disordered c-Myc bHLH-LZ domain to enable label-free, in situ, and long-term measurements at the single-molecule level. We use the device to study c-Myc interaction with Max and/or small molecule inhibitors. We observe the self-folding/unfolding process of c-Myc and reveal its interaction mechanism with Max and inhibitors through ultrasensitive real-time monitoring. We capture a relatively stable encounter intermediate ensemble of c-Myc during its transition from the unbound state to the fully folded state. The c-Myc/Max and c-Myc/inhibitor dissociation constants derived are consistent with other ensemble experiments. These proof-of-concept results provide an understanding of the IDP-binding/folding mechanism and represent a promising nanotechnology for IDP conformation/interaction studies and drug discovery.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2023
Tipo de documento:
Article