A rationally-designed chimeric KDM1A/KDM1B histone demethylase tower domain deletion mutant retaining enzymatic activity.
A target with therapeutic potential, lysine-specific demethylase 1A (KDM1A) is a regulator of gene expression whose tower domain is a protein-protein interaction motif. This domain facilitates the interaction of KDM1A with coregulators and multiprotein complexes that direct its activity to nucleosomes. We describe the design and characterization of a chimeric 'towerless' KDM1A, termed nΔ150 KDM1AΔTower KDM1B chimera (chKDM1AΔTower), which incorporates a region from the paralog lysine-specific demethylase 1B (KDM1B). This chimera copurifies with FAD and displays demethylase activity, but fails to bind the partner protein corepressor of the RE1-silencing transcription factor (CoREST). We conclude that KDM1A catalysis can be decoupled from tower-dependent interactions, lending chKDM1AΔTower useful for dissecting molecular contributions to KDM1A function.
Duke Scholars
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Related Subject Headings
- Sequence Deletion
- Recombinant Fusion Proteins
- Protein Structure, Tertiary
- Protein Engineering
- Molecular Sequence Data
- Models, Molecular
- Humans
- Histone Demethylases
- Biochemistry & Molecular Biology
- Amino Acid Sequence
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Sequence Deletion
- Recombinant Fusion Proteins
- Protein Structure, Tertiary
- Protein Engineering
- Molecular Sequence Data
- Models, Molecular
- Humans
- Histone Demethylases
- Biochemistry & Molecular Biology
- Amino Acid Sequence