1. CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission
- Author
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Claudia Cericola, Alberto Luini, Alessandra Pesce, Daniela Corda, Enrico Millo, Anna Maria Massaro, Stefania Spanò, Martino Bolognesi, and Marco Nardini
- Subjects
Models, Molecular ,Protein Folding ,Transcription, Genetic ,Recombinant Fusion Proteins ,Molecular Sequence Data ,Golgi Apparatus ,Peptide binding ,Biology ,Crystallography, X-Ray ,General Biochemistry, Genetics and Molecular Biology ,symbols.namesake ,chemistry.chemical_compound ,Protein structure ,Membrane fission ,Animals ,Amino Acid Sequence ,Binding site ,Molecular Biology ,Transcription factor ,Golgi membrane ,Binding Sites ,General Immunology and Microbiology ,General Neuroscience ,Cell Membrane ,Articles ,Golgi apparatus ,Brefeldin A ,NAD ,Protein Structure, Tertiary ,Rats ,Cell biology ,Repressor Proteins ,chemistry ,Biochemistry ,symbols ,Acyl Coenzyme A ,Acyl-CoA ,Transcription co-repression ,Carrier Proteins ,Peptides ,Sequence Alignment ,Protein Binding ,Transcription Factors - 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.
- Published
- 2003
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