Abstract
BackgroundThe B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. It has long been thought that the groove dimensions depend on the DNA sequence, however this relationship has remained elusive. Here, our aim is to elucidate how the DNA sequence intrinsically shapes the grooves.Methodology/Principal FindingsThe present study is based on the analysis of datasets of free and protein-bound DNA crystal structures, and from a compilation of NMR 31P chemical shifts measured on free DNA in solution on a broad range of representative sequences. The 31P chemical shifts can be interpreted in terms of the BI↔BII backbone conformations and dynamics. The grooves width and depth of free and protein-bound DNA are found to be clearly related to the BI/BII backbone conformational states. The DNA propensity to undergo BI↔BII backbone transitions is highly sequence-dependent and can be quantified at the dinucleotide level. This dual relationship, between DNA sequence and backbone behavior on one hand, and backbone behavior and groove dimensions on the other hand, allows to decipher the link between DNA sequence and groove dimensions. It also firmly establishes that proteins take advantage of the intrinsic DNA groove properties.Conclusions/SignificanceThe study provides a general framework explaining how the DNA sequence shapes the groove dimensions in free and protein-bound DNA, with far-reaching implications for DNA-protein indirect readout in both specific and non specific interactions.
Highlights
The cellular DNA is continuously ‘‘read’’ by proteins
The B-DNA intrinsic mechanics involves a tight relationship between the backbone conformations and the inter base-pair rotational parameters of roll and twist [21,28,30,31,32,33,39]
We investigate the relationship between the phosphate group conformations and the groove dimensions, including the major and minor groove widths
Summary
The cellular DNA is continuously ‘‘read’’ by proteins. DNAprotein interactions are informed by the intrinsic mechanical properties of DNA, which facilitate its deformation in the complex. The DNA binding process depends on the intrinsic ability of free DNA to adopt its structure when bound to a protein. Architectural proteins [1] and proteins binding DNA sequences non- [9] mainly interact with the DNA minor groove, where there is little discrimination between base types [10]. This type of interaction is still intriguing since the DNA minor groove is often presumed too narrow to accommodate protein structural elements without energetically costly distortions. The B-DNA major and minor groove dimensions are crucial for DNA-protein interactions. Our aim is to elucidate how the DNA sequence intrinsically shapes the grooves
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