The transition state for protein-DNA recognition

FERREIRO, D.U.; SANCHEZ, I; PRAT GAY G. DE

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Año: 2008 vol. 105 p. 10797 - 10802

0027-8424

We describe the formation of protein–DNA contacts in the twostateroute for DNA sequence recognition by a transcriptionalregulator. Surprisingly, direct sequence readout establishes in thetransition state and constitutes the bottleneck of complex formation.Although a few nonspecific ionic interactions are formed atthis early stage, they mainly play a stabilizing role in the finalconsolidated complex. The interface is fairly plastic in the transitionstate, likely because of a high level of hydration. The overall pictureof this two-state route largely agrees with a smooth energylandscape for binding that speeds up DNA recognition. This ‘‘direct’’two-state route differs from the parallel multistep pathwaydescribed for this system, which involves nonspecific contacts andat least two intermediate species that must involve substantialconformational rearrangement in either or both macromolecules.