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Transition state for protein-DNA recognition.

ABSTRACT: 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.

SUBMITTER: Ferreiro DU

PROVIDER: S-EPMC2504826 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Transition state for protein-DNA recognition.

Ferreiro Diego U DU Sánchez Ignacio E IE de Prat Gay Gonzalo G

Proceedings of the National Academy of Sciences of the United States of America 20080729 31

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 ...[more]

PMID: 18664582

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