Structural code for DNA recognition revealed in crystal structures of papillomavirus E2-DNA targets

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.