Experimental snapshots of a protein-DNA binding landscape.
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.
Sánchez
Ignacio E
IE
Protein Structure-Function and Engineering Laboratory, Fundación Instituto Leloir and Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Ferreiro
Diego U
DU
Dellarole
Mariano
M
de Prat-Gay
Gonzalo
G
D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D057054:Molecular Imaging / Q000379:methods; D009154:Mutation / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
D004268:DNA-Binding Proteins; D009856:Oncogene Proteins, Viral; C076036:oncogene protein E2, Human papillomavirus type 1; D004247:DNA