期刊
NUCLEIC ACIDS RESEARCH
卷 44, 期 22, 页码 11024-11032出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw1010
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资金
- Danish Council for Independent Research [DFF-0602-, 0602-01778B]
- Lundbeck Foundation
- Novo Nordisk Foundation [NNF] [15OC00012345]
- European Union [661415]
- Novo Nordisk Foundation
- Marie Curie Actions (MSCA) [661415] Funding Source: Marie Curie Actions (MSCA)
- Novo Nordisk Fonden [NNF15OC0017956] Funding Source: researchfish
G-quadruplexes (G4s) are DNA secondary structures that are capable of forming and function in vivo. The propensity of G4s to exhibit extreme polymorphism and complex dynamics is likely to influence their cellular function, yet a clear microscopic picture of their folding process is lacking. Here we employed single-molecule FRET microscopy to obtain a direct view of the folding and underlying conformational dynamics of G4s formed by the human telomeric sequence in potassium containing solutions. Our experiments allowed detecting several folded states that are populated in the course of G4 folding and determining their folding energetics and timescales. Combining the single-molecule data with molecular dynamics simulations enabled obtaining a structural description of the experimentally observed folded states. Our work thus provides a comprehensive thermodynamic and kinetic description of the folding of G4s that proceeds through a complex multi-route pathway, involving several marginally stable conformational states.
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