CtBP1/BARS Gly172-->Glu mutant structure: impairing NAD(H)-binding and dimerization.
C-terminal binding proteins (CtBPs) are multi-functional proteins involved in nuclear transcriptional co-repression, Golgi membrane fission, and synaptic ribbon formation. Binding of NAD(H) to CtBPs promotes dimerization. CtBP dimers act as a scaffold for multimeric protein complex formation, thus bridging transcriptional repressors and their targets in the nucleus. Based on size-exclusion chromatography experiments and on the crystal structure of the NAD(H)-free G172E CtBP mutant, we show here that absence of NAD(H) induces flexibility/backbone conformational changes at the dimerization interface and at the CtBP interdomain region. The results presented shed first light on the correlation between NAD(H)-binding and functional CtBP dimerization.
Department of Biomolecular Sciences and Biotechnology, CNR-INFM and CIMAINA, University of Milano, Via Celoria 26, I-20133 Milano, Italy.
Marco
M
Nardini
Carmen
C
Valente
Stefano
S
Ricagno
Alberto
A
Luini
Daniela
D
Corda
Martino
M
Bolognesi
D019943:Amino Acid Substitution; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D005998:Glycine / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009243:NAD / Q000378:metabolism*; D011487:Protein Conformation; D055503:Protein Multimerization; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; C119945:Ctbp1 protein, rat; D014157:Transcription Factors; D009243:NAD; D018698:Glutamic Acid; D005998:Glycine