Abstract
C-terminal-binding protein/brefeldin A-ADP ribosylated substrate (CtBP/BARS) plays key roles in development and oncogenesis as a transcription co-repressor, and in intracellular traffic as a promoter of Golgi membrane fission. Co-repressor activity is regulated by NAD(H) binding to CtBP/BARS, while membrane fission is associated with its acyl-CoA-dependent acyltransferase activity. Here, we report the crystal structures of rat CtBP/BARS in a binary complex with NAD(H), and in a ternary complex with a PIDLSKK peptide mimicking the consensus motif (PXDLS) recognized in CtBP/BARS cellular partners. The structural data show CtBP/BARS in a NAD(H)-bound dimeric form; the peptide binding maps the recognition site for DNA-binding proteins and histone deacetylases to an N-terminal region of the protein. The crystal structure together with the site-directed mutagenesis data and binding experiments suggest a rationale for the molecular mechanisms underlying the two fundamental co-existing, but diverse, activities supported by CtBP/BARS in the nucleus and in Golgi membranes.
Original language | English |
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Pages (from-to) | 3122-30 |
Number of pages | 9 |
Journal | EMBO Journal |
Volume | 22 |
Issue number | 12 |
DOIs | |
Publication status | Published - 16 Jun 2003 |
Keywords
- Acyl Coenzyme A
- Amino Acid Sequence
- Animals
- Binding Sites
- Carrier Proteins
- Cell Membrane
- Crystallography, X-Ray
- Golgi Apparatus
- Models, Molecular
- Molecular Sequence Data
- NAD
- Peptides
- Protein Binding
- Protein Folding
- Protein Structure, Tertiary
- Rats
- Recombinant Fusion Proteins
- Repressor Proteins
- Sequence Alignment
- Transcription Factors
- Transcription, Genetic