Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 17, Pages 7751-7756Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911734107
Keywords
energy landscape; human papillomavirus E2 protein; kinetic trap; kinetics; protein-DNA interaction
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Funding
- Welcome Trust [GR077355AYA]
- Agencia Nacional de Promocion Cientifica y Tecnologica [PICT 2000 01-08959]
- Consejo Nacional de Investigaciones Cientificas y Tecnicas
- Agencia Espanola de Cooperacion Inter-nacional
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Protein recognition of DNA sites is a primary event for gene function. Its ultimate mechanistic understanding requires an integrated structural, dynamic, kinetic, and thermodynamic dissection that is currently limited considering the hundreds of structures of protein-DNA complexes available. We describe a protein-DNA-binding pathway in which an initial, diffuse, transition state ensemble with some nonnative contacts is followed by formation of extensive nonnative interactions that drive the system into a kinetic trap. Finally, nonnative contacts are slowly rearranged into native-like interactions with the DNA backbone. Dissimilar protein-DNA interfaces that populate along the DNA-binding route are explained by a temporary degeneracy of protein-DNA interactions, centered on dual-role residues. The nonnative species slow down the reaction allowing for extended functionality.
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