CH/pi interactions in the crystal structure of TATA-box binding protein/DNA complexes

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• TATA box-binding proteins (TBP) are crucial transcription factors that recognize and bind to the TATA box sequence in promoter DNA.
• The precise molecular interactions mediating TBP-promoter DNA binding have been a subject of extensive research.
• Previous studies suggested nonpolar forces at the interface, but their specific nature remained unclear.

Purpose of the Study:

• To analyze the crystal structures of TBP-promoter DNA complexes to elucidate the molecular interactions involved in binding.
• To identify and characterize specific nonpolar contacts between TBP and the TATA box DNA.
• To attribute the observed nonpolar forces to a specific type of interaction, namely CH/pi interactions.

Main Methods:

• Analysis of crystal structures of TBP-promoter DNA complexes from various sources.
• Utilized a custom program, CHPI, for detailed structural analysis.
• Focused on identifying short contacts at the interface between TBP and the TATA box minor groove.

Main Results:

• Identified numerous short CH/Csp2 contacts at the boundary of TBP and the TATA box minor groove.
• Attributed previously reported nonpolar forces to CH/pi interactions.
• Discovered multiple CH/pi contacts within the same strand of the promoter DNA.
• Observed that the TATA element is partially unwound and severely bent upon complexation.
• Determined that CH/pi interactions stabilize the bent and unwound DNA structure, with H2' of deoxyribose and thymine's methyl group being critical.

Conclusions:

• CH/pi interactions are a significant component of the nonpolar forces governing TBP-promoter DNA binding.
• These interactions play a crucial role in stabilizing the distorted DNA structure induced by TBP binding.
• Specific molecular features, including the deoxyribose H2' and thymine methyl group, are key participants in these stabilizing interactions.