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.
|Titolo:||CtBP/BARS: a dual-function protein involved in transcriptional co-repression, and Golgi membrane fission|
|Autori interni:||BOLOGNESI, MARTINO (Ultimo)|
NARDINI, MARCO (Primo)
|Parole Chiave:||Acyl-CoA; Brefeldin A; Golgi membrane; NAD; Transcription co-repression|
|Data di pubblicazione:||giu-2003|
|Digital Object Identifier (DOI):||10.1093/emboj/cdg283|
|Appare nelle tipologie:||01 - Articolo su periodico|