Inherent DNA curvature and flexibility correlate with TATA box functionality

• Published in: BIOPOLYM Vol. 46; no. 6; pp. 403 - 415
• Main Authors: Norberto de Souza, Osmar, Ornstein, Rick L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.1998
• Subjects: Adenoviridae - genetics; Base Pairing; Crystal structure; DNA curvature; DNA flexibility; DNA, Viral - chemistry; DNA-Binding Proteins - chemistry; Molecular dynamics; Molecular structure; Mutation - genetics; Nucleic Acid Conformation; Promoter Regions, Genetic - genetics; Proteins; TATA Box - physiology; TATA box binding protein (TBP); TATA box functionality; TATA-Box Binding Protein; TBP binding; TBP recognition; TBP transcriptional activation; Transcription Factors - chemistry; Transcription, Genetic - genetics; X-Ray Diffraction
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/(SICI)1097-0282(199811)46:6<403::AID-BIP5>3.0.CO;2-A

Four 1.5 ns molecular dynamics (MD) simulations were performed on the d(GCTATAAAAGGG) · d(CCCTTTTATAGC) double helix dodecamer bearing the Adenovirus major late promoter TATA element and three iso‐composition mutants for which physical and biochemical data are available from the same laboratory. Three of these DNA sequences experimentally induce tight binding with the TATA box binding protein (TBP) and induce high transcription rates; the other DNA sequence induces much lower TBP binding and transcription. The x‐ray crystal structures have previously shown that the duplex DNA in DNA–TBP complexes are highly bent. We performed and analyzed MD simulations for these four DNAs, whose experimental structures are not available, in order to address the issue of whether inherent DNA structure and flexibility play a role in establishing these observed preferences. A comparison of the experimental and simulated results demonstrated that DNA duplex sequence‐dependent curvature and flexibility play a significant role in TBP recognition, binding, and transcriptional activation. © 1998 John Wiley & Sons, Inc. Biopoly 46: 403–415, 1998