CtBP/BARS

a dual-function protein involved in transcription co-repression and Golgi membrane fission

Marco Nardini, Stefania Spanò, Claudia Cericola, Alessandra Pesce, Anna Massaro, Enrico Millo, Alberto Luini, Daniela Corda, Martino Bolognesi

Research output: Contribution to journalArticle

114 Citations (Scopus)

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 languageEnglish
Pages (from-to)3122-30
Number of pages9
JournalEMBO Journal
Volume22
Issue number12
DOIs
Publication statusPublished - 16 Jun 2003

Fingerprint

Brefeldin A
Transcription
Adenosine Diphosphate
Membranes
Substrates
NAD
Co-Repressor Proteins
Proteins
Crystal structure
Acyltransferases
Acyl Coenzyme A
Mutagenesis
Peptides
Histone Deacetylases
DNA-Binding Proteins
Site-Directed Mutagenesis
C-terminal binding protein
Rats
Carcinogenesis

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

Cite this

Nardini, M., Spanò, S., Cericola, C., Pesce, A., Massaro, A., Millo, E., ... Bolognesi, M. (2003). CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission. EMBO Journal, 22(12), 3122-30. https://doi.org/10.1093/emboj/cdg283

CtBP/BARS : a dual-function protein involved in transcription co-repression and Golgi membrane fission. / Nardini, Marco; Spanò, Stefania; Cericola, Claudia; Pesce, Alessandra; Massaro, Anna; Millo, Enrico; Luini, Alberto; Corda, Daniela; Bolognesi, Martino.

In: EMBO Journal, Vol. 22, No. 12, 16.06.2003, p. 3122-30.

Research output: Contribution to journalArticle

Nardini, M, Spanò, S, Cericola, C, Pesce, A, Massaro, A, Millo, E, Luini, A, Corda, D & Bolognesi, M 2003, 'CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission', EMBO Journal, vol. 22, no. 12, pp. 3122-30. https://doi.org/10.1093/emboj/cdg283
Nardini M, Spanò S, Cericola C, Pesce A, Massaro A, Millo E et al. CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission. EMBO Journal. 2003 Jun 16;22(12):3122-30. https://doi.org/10.1093/emboj/cdg283
Nardini, Marco ; Spanò, Stefania ; Cericola, Claudia ; Pesce, Alessandra ; Massaro, Anna ; Millo, Enrico ; Luini, Alberto ; Corda, Daniela ; Bolognesi, Martino. / CtBP/BARS : a dual-function protein involved in transcription co-repression and Golgi membrane fission. In: EMBO Journal. 2003 ; Vol. 22, No. 12. pp. 3122-30.
@article{4a815b5c119e4949bbbd580922c6e480,
title = "CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission",
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.",
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",
author = "Marco Nardini and Stefania Span{\`o} and Claudia Cericola and Alessandra Pesce and Anna Massaro and Enrico Millo and Alberto Luini and Daniela Corda and Martino Bolognesi",
year = "2003",
month = "6",
day = "16",
doi = "10.1093/emboj/cdg283",
language = "English",
volume = "22",
pages = "3122--30",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - CtBP/BARS

T2 - a dual-function protein involved in transcription co-repression and Golgi membrane fission

AU - Nardini, Marco

AU - Spanò, Stefania

AU - Cericola, Claudia

AU - Pesce, Alessandra

AU - Massaro, Anna

AU - Millo, Enrico

AU - Luini, Alberto

AU - Corda, Daniela

AU - Bolognesi, Martino

PY - 2003/6/16

Y1 - 2003/6/16

N2 - 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.

AB - 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.

KW - Acyl Coenzyme A

KW - Amino Acid Sequence

KW - Animals

KW - Binding Sites

KW - Carrier Proteins

KW - Cell Membrane

KW - Crystallography, X-Ray

KW - Golgi Apparatus

KW - Models, Molecular

KW - Molecular Sequence Data

KW - NAD

KW - Peptides

KW - Protein Binding

KW - Protein Folding

KW - Protein Structure, Tertiary

KW - Rats

KW - Recombinant Fusion Proteins

KW - Repressor Proteins

KW - Sequence Alignment

KW - Transcription Factors

KW - Transcription, Genetic

U2 - 10.1093/emboj/cdg283

DO - 10.1093/emboj/cdg283

M3 - Article

VL - 22

SP - 3122

EP - 3130

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 12

ER -