Work

Experimental snapshots of a protein-DNA binding landscape

Year: 2010

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0911734107

Authors: Ignacio E. Sánchez, Diego U. Ferreiro, Mariano Dellarole, Gonzalo de Prat-Gay

Institutions: Consejo Nacional de Investigaciones Científicas y Técnicas, Fundación Instituto Leloir, National University of Quilmes

Language: English

Topic: Diffusion and Search Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: Wellcome Trust

Award: G427009959