Transition state for protein-DNA recognition.
We describe the formation of protein-DNA contacts in the two-state route for DNA sequence recognition by a transcriptional regulator. Surprisingly, direct sequence readout establishes in the transition state and constitutes the bottleneck of complex formation. Although a few nonspecific ionic interactions are formed at this early stage, they mainly play a stabilizing role in the final consolidated complex. The interface is fairly plastic in the transition state, likely because of a high level of hydration. The overall picture of this two-state route largely agrees with a smooth energy landscape for binding that speeds up DNA recognition. This "direct" two-state route differs from the parallel multistep pathway described for this system, which involves nonspecific contacts and at least two intermediate species that must involve substantial conformational rearrangement in either or both macromolecules.
Ferreiro
Diego U
DU
Fundación Instituto Leloir and Instituto de Investigaciones Bioquímicas de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Patricias Argentinas 435, 1405 Buenos Aires, Argentina.
Sánchez
Ignacio E
IE
de Prat Gay
Gonzalo
G
D004247:DNA / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D027383:Papillomaviridae / Q000378:metabolism*; D011485:Protein Binding; D013816:Thermodynamics; D014157:Transcription Factors / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000378:metabolism*
D014157:Transcription Factors; D014759:Viral Envelope Proteins; D004247:DNA