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

EMBO J. 2003 Jun 16;22(12):3122-30. doi: 10.1093/emboj/cdg283.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Membrane / metabolism*
  • Crystallography, X-Ray
  • Golgi Apparatus / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • NAD / chemistry
  • NAD / metabolism
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / chemistry*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors*
  • Transcription, Genetic*

Substances

  • Acyl Coenzyme A
  • Carrier Proteins
  • Ctbp1 protein, rat
  • Peptides
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factors
  • NAD