Importance of DNA stiffness in protein-DNA binding specificity

From the first high-resolution structure of a repressor bound specifically to its DNA recognition sequence it has been shown that the phage 434 repressor protein binds as a dimer to the helix. Tight, local interactions are made at the ends of the binding site, causing the central four base pairs (bp...

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Bibliographic Details
Published in:Nature (London) 1987-09, Vol.329 (6136), p.263-266
Main Authors: Hogan, M. E, Austin, R. H
Format: Article
Language:English
Subjects:
Base Sequence
Binding Sites
Biological and medical sciences
Chemical Phenomena
Chemistry, Physical
Deoxyribonucleic acid
DNA
DNA - metabolism
Elastic properties
Fundamental and applied biological sciences. Psychology
Genetics
Interactions. Associations
Intermolecular phenomena
Macromolecular Substances
Mathematics
Models, Biological
Molecular biophysics
Nucleic Acid Conformation
Protein Binding
Repressor Proteins - metabolism
Structure-Activity Relationship
Transcription Factors - metabolism
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Summary:From the first high-resolution structure of a repressor bound specifically to its DNA recognition sequence it has been shown that the phage 434 repressor protein binds as a dimer to the helix. Tight, local interactions are made at the ends of the binding site, causing the central four base pairs (bp) to become bent and overtwisted. The centre of the operator is not in contact with protein but repressor binding affinity can be reduced at least 50-fold in response to a sequence change there. This observation might be explained should the structure of the intervening DNA segment vary with its sequence, or if DNA at the centre of the operator resists the torsional and bending deformation necessary for complex formation in a sequence dependent fashion. We have considered the second hypothesis by demonstrating that DNA stiffness is sequence dependent. A method is formulated for calculating the stiffness of any particular DNA sequence, and we show that this predicted relationship between sequence and stiffness can explain the repressor binding data in a quantitative manner. We propose that the elastic properties of DNA may be of general importance to an understanding of protein-DNA binding specificity.
ISSN:0028-0836
1476-4687
DOI:10.1038/329263a0