A TeZla micromixer for interrogating the early and broad folding landscape of G-quadruplex via multistage velocity descending.
Proc Natl Acad Sci U S A
; 121(4): e2315401121, 2024 Jan 23.
Article
em En
| MEDLINE
| ID: mdl-38232280
ABSTRACT
Biomacromolecular folding kinetics involves fast folding events and broad timescales. Current techniques face limitations in either the required time resolution or the observation window. In this study, we developed the TeZla micromixer, integrating Tesla and Zigzag microstructures with a multistage velocity descending strategy. TeZla achieves a significant short mixing dead time (40 µs) and a wide time window covering four orders of magnitude (up to 300 ms). Using this unique micromixer, we explored the folding landscape of c-Myc G4 and its noncanonical-G4 derivatives with different loop lengths or G-vacancy sites. Our findings revealed that c-Myc can bypass folding intermediates and directly adopt a G4 structure in the cation-deficient buffer. Moreover, we found that the loop length and specific G-vacancy site could affect the folding pathway and significantly slow down the folding rates. These results were also cross-validated with real-time NMR and circular dichroism. In conclusion, TeZla represents a versatile tool for studying biomolecular folding kinetics, and our findings may ultimately contribute to the design of drugs targeting G4 structures.
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Base de dados:
MEDLINE
Assunto principal:
Quadruplex G
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article