Related Experiment Video
Updated: Jul 24, 2026
14:25
Method for Efficient Refolding and Purification of Chemoreceptor Ligand Binding Domain
Published on: December 12, 2017
Conformational model for binding site recognition by the E.coli MetJ transcription factor
R Liu1, T W Blackwell, D J States
1Center for Computational Biology and Department of Genetics, Washington University School of Medicine, 700 S. Euclid Ave, St Louis, MO 63110, USA.
Bioinformatics (Oxford, England)
|July 13, 2001
Summary
This study introduces a novel DNA conformation model to improve transcription factor binding site identification. The hybrid model enhances prediction accuracy and reduces false positives, discovering new binding sites in E. coli.
Area of Science:
- Molecular Biology
- Bioinformatics
- Structural Biology
Background:
- Current methods for identifying DNA sequence-specific binding sites, like position-specific weight matrices, lack sensitivity and specificity.
- DNA's double helix exhibits sequence-dependent conformational variations influencing macromolecular interactions.
- These conformational variations are hypothesized to play a role in transcription factor binding site recognition.
Purpose of the Study:
- To develop and validate a computational model incorporating DNA conformational information for improved transcription factor binding site prediction.
- To enhance the predictive power of existing models by integrating sequence and structure data.
- To identify novel functional transcription factor binding sites within a genome.
Main Methods:
- Development of sequence-dependent DNA helix distortion conformation models.
- Definition of a tertiary structure template for the MetJ repressor binding site using these models.
- Creation of a hybrid model combining conformational and primary sequence profile data.
- Genome-wide search of E. coli using the hybrid model.
Main Results:
- The conformational model identified distinct features of protein binding sites compared to sequence-based profiles.
- A hybrid model integrating conformational and sequence data demonstrated improved discriminatory power.
- The hybrid model successfully identified known MetJ binding sites in E. coli.
- Several novel MetJ binding sites were discovered, including upstream of metK and abc genes, with a significantly lower false positive rate than sequence profile methods.
Conclusions:
- Incorporating DNA conformational information significantly enhances the accuracy of transcription factor binding site prediction.
- The developed hybrid model offers a more sensitive and specific approach for identifying regulatory elements.
- This method facilitates the discovery of novel functional binding sites, advancing our understanding of gene regulation.
Related Concept Videos
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:58Cooperative Allosteric Transitions
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
02:13Cooperative Binding of Transcription Regulators
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
01:27Chemotaxis in E. coli
Chemotaxis in Escherichia coli is a sensory-driven motility mechanism that enables bacteria to navigate chemical gradients, moving toward beneficial environments while avoiding harmful conditions. This process relies on a signal transduction system integrating external chemical cues with flagellar motor control.Chemoreceptors and Signal DetectionE. coli detects chemical gradients through methyl-accepting chemotaxis proteins (MCPs), which are membrane-bound chemoreceptors that sense attractants...