DNA deformability as a recognition feature in the reverb response element.

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• Nuclear receptors are transcription factors that regulate gene expression.
• Most nuclear receptors recognize the same DNA sequence (AGGTCA).
• Understanding how nuclear receptors distinguish between similar DNA sequences is crucial.

Purpose of the Study:

• To investigate how the Rev-Erb nuclear receptor distinguishes its DNA binding sites.
• To analyze the structural basis of Rev-Erb-DNA interactions and DNA distortions.

Main Methods:

• X-ray crystallography to determine Rev-Erb-DNA complex structures.
• Analysis of protein-DNA interactions and DNA structural deformations.

Main Results:

• A consistent DNA distortion was observed at a TA step preceding the Rev-Erb binding sequence.
• Rev-Erb does not form sequence-specific contacts with this TA site.
• Rev-Erb utilizes the intrinsic geometry and flexibility of the TA site for high-affinity binding.

Conclusions:

• DNA sequence-dependent deformations play a role in nuclear receptor binding site discrimination.
• Rev-Erb's binding mechanism highlights the importance of DNA shape and flexibility.
• This mechanism may be shared by other monomeric nuclear receptors like NGFI-B, SF-1, and ROR.