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DNA sequence and structure: direct and indirect recognition in protein-DNA binding
N R Steffen1, S D Murphy, L Tolleri
1Information and Computer Science, University of California, Irvine, Irvine, CA, 92697-3425, USA. nsteffen@uci.edu
Bioinformatics (Oxford, England)
|August 10, 2002
Summary
Computational modeling of DNA-protein interactions reveals that structural DNA properties, not just base sequences, drive protein binding specificity. This finding advances our understanding of indirect recognition in DNA-binding proteins.
Area of Science:
- Structural Biology
- Bioinformatics
- Computational Biology
Background:
- Proteins recognize DNA sequences directly via base-specific amino acid interactions.
- Proteins also use indirect recognition, sensing DNA structural properties for sequence specificity.
Purpose of the Study:
- To investigate if threading DNA onto crystal structures explains indirect recognition.
- To determine if structure-based motifs can be represented as sequence-based motifs.
Main Methods:
- Utilized a crystal structure of E. coli integration host factor (IHF) bound to DNA.
- Threaded DNA sequences onto the structure to analyze binding site separation and affinity.
- Transformed structural motifs into various sequence-based representations (e.g., weight matrices, alignments).
Main Results:
- Threading DNA onto the IHF structure significantly separated binding sites from random sequences.
- Structural motifs were algorithmically converted into sequence motifs (e.g., weight matrices, alignments).
- These sequence motifs also showed significant separation and correlated with binding affinity.
Conclusions:
- Deformation energy contributes to indirect recognition in DNA-protein binding.
- Indirect recognition partially explains the sequence specificity of proteins like IHF.
- Structural information is crucial for understanding DNA-binding protein specificity.