Dna Sequence-specific Recognition by a Transcriptional Regulator Requires Indirect Readout of A-tracts.
From: Instituto de Biología Molecular Eladio Viñuela (CSIC), Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma, Canto Blanco, 28049 Madrid, Spain.
Nucleic acids research
- Publish Date: 2007
- ISSN: 1362-4962
- Volume: 35
- Issue: 10
- Pages: 3252-61
- Medium: Internet
- Language: English
- Citation (JAMA): Mendieta Jesús, Pérez-Lago Laura, Salas Margarita, et al. Dna Sequence-specific Recognition by a Transcriptional Regulator Requires Indirect Readout of A-tracts.. Nucleic Acids Res. 2007;35:3252-61
Abstract
The bacteriophage Ø29 transcriptional regulator p4 binds to promoters of different intrinsic activities. The p4-DNA complex contains two identical protomers that make similar interactions with the target sequence 5’-AACTTTTT-15 bp-AAAATGTT-3’. To define how the various elements in the target sequence contribute to p4’s affinity, we studied p4 binding to a series of mutated binding sites. The binding specificity depends critically on base pairs of the target sequence through both direct as well as indirect readout. There is only one specific contact between a base and an amino acid residue; other contacts take place with the phosphate backbone. Alteration of direct amino acid-base contacts, or mutation of non-contacted A.T base pairs at A-tracts abolished binding. We generated three 5 ns molecular dynamics (MD) simulations to investigate the basis for the p4-DNA complex specificity. Recognition is controlled by the protein and depends on DNA dynamic properties. MD results on protein-DNA contacts and the divergence of p4 affinity to modified binding sites reveal an inherent asymmetry, which is required for p4-specific binding and may be crucial for transcription regulation.
Mesh Headings (Keywords): Bacillus Phages, Base Sequence, Binding Sites, Computer Simulation, DNA, Viral, Models, Molecular, Mutation, Nucleic Acid Conformation, Promoter Regions (Genetics), Protein Binding, Repetitive Sequences, Nucleic Acid, Transcription Factors, Viral Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 17452358
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.