CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission

AUTOR(ES)

Nardini, Marco

FONTE

Oxford University Press

RESUMO

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.

Documentos Relacionados

• Escherichia coli 6S RNA gene is part of a dual-function transcription unit.
• Dual-Function Vaccine for Pseudomonas aeruginosa: Characterization of Chimeric Exotoxin A-Pilin Protein
• Role of a Cytoplasmic Dual-function Glycosyltransferase in O2 Regulation of Development in Dictyostelium*
• An autoregulated dual-function antitat gene for human immunodeficiency virus type 1 gene therapy.
• Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague▿