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Experimental snapshots of a protein-DNA binding landscape.

ABSTRACT: 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.

SUBMITTER: Sanchez IE

PROVIDER: S-EPMC2867883 | biostudies-other | 2010 Apr

REPOSITORIES: biostudies-other

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Experimental snapshots of a protein-DNA binding landscape.

Sánchez Ignacio E IE Ferreiro Diego U DU Dellarole Mariano M de Prat-Gay Gonzalo G

Proceedings of the National Academy of Sciences of the United States of America 20100407 17

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 syst ...[more]

PMID: 20375284

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