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Structural code for DNA recognition revealed in crystal structures of papillomavirus E2-DNA targets
H Rozenberg1, D Rabinovich, F Frolow
1Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Abstract:
Transcriptional regulation in papillomaviruses depends on sequence-specific binding of the regulatory protein E2 to several sites in the viral genome. Crystal structures of bovine papillomavirus E2 DNA targets reveal a conformational variant of B-DNA characterized by a roll-induced writhe and helical repeat of 10.5 bp per turn. A comparison between the free and the protein-bound DNA demonstrates that the intrinsic structure of the DNA regions contacted directly by the protein and the deformability of the DNA region that is not contacted by the protein are critical for sequence-specific protein/DNA recognition and hence for gene-regulatory signals in the viral system. We show that the selection of dinucleotide or longer segments with appropriate conformational characteristics, when positioned at correct intervals along the DNA helix, can constitute a structural code for DNA recognition by regulatory proteins. This structural code facilitates the formation of a complementary protein-DNA interface that can be further specified by hydrogen bonds and nonpolar interactions between the protein amino acids and the DNA bases.
Insights
Papillomavirus gene regulation relies on the E2 protein binding specific DNA sequences. DNA structure and flexibility are key to this recognition, revealing a "structural code" for protein-DNA interactions.
Area of Science:
- Molecular Biology
- Structural Biology
- Virology
Background:
- Transcriptional regulation in papillomaviruses is mediated by the sequence-specific binding of the regulatory protein E2.
- The E2 protein interacts with multiple sites within the viral genome to control gene expression.
Purpose of the Study:
- To elucidate the structural basis of sequence-specific protein-DNA recognition in papillomaviruses.
- To understand how DNA conformation and deformability contribute to the binding of the E2 regulatory protein.
Main Methods:
- Determined crystal structures of bovine papillomavirus E2 protein bound to its DNA targets.
- Compared the structures of free and protein-bound DNA to analyze conformational changes.
- Investigated the role of intrinsic DNA structure and deformability in protein-DNA interactions.
Main Results:
- Papillomavirus E2 DNA targets adopt a unique B-DNA conformation with a roll-induced writhe and a helical repeat of 10.5 bp/turn.
- Both the intrinsic structure of directly contacted DNA and the deformability of uncontacted DNA are crucial for E2 recognition.
- A 'structural code' involving specific dinucleotide or longer DNA segments at defined intervals facilitates protein recognition.
Conclusions:
- Sequence-specific DNA recognition by regulatory proteins like E2 is governed by a structural code embedded in DNA conformation.
- This structural code enables the formation of a complementary protein-DNA interface through specific interactions.
- Understanding this code is critical for deciphering gene-regulatory signals in viral systems.