CECR2 Bromodomain's Binding Preferences for Acetylated Histones and Non-Histone Ligands
Author Information
Author(s): Phillips Margaret, Cook Elizabeth D., Marunde Matthew R., Tonelli Marco, Khan Laiba, Henrickson Amy, Lignos James M., Stein Janet L., Stein Gary S., Frietze Seth, Demeler Borries, Glass Karen C.
Primary Institution: University of Vermont
Hypothesis
The CECR2 bromodomain selectively recognizes acetylated histone proteins and non-histone ligands through distinct binding modes.
Conclusion
The CECR2 bromodomain exhibits a strong preference for multi-acetylated histone ligands and interacts with acetylated RelA in a unique manner.
Supporting Evidence
- The CECR2 bromodomain selectively binds acetylated histone H3 and H4 ligands, with the highest affinity for tetra-acetylated histone H4.
- Neighboring post-translational modifications, including methylation and phosphorylation, modulate acetyllysine recognition.
- The CECR2 bromodomain binds to acetylated RelA with micromolar affinity, using a distinctive binding mode.
- Functional mutagenesis highlighted critical residues in ligand specificity and binding dynamics.
Takeaway
This study shows that a specific protein can tell the difference between modified and unmodified parts of other proteins, which is important for how genes are turned on and off.
Methodology
The study used isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) spectroscopy, and a high-throughput peptide assay to analyze binding interactions.
Limitations
The study focuses on the bromodomain in isolation, which may not fully represent its interactions in the context of the full-length protein.
Digital Object Identifier (DOI)
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