Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex
AUTOR(ES)
Brzovic, Peter S.
FONTE
The National Academy of Sciences
RESUMO
BRCA1 is a breast and ovarian cancer tumor suppressor protein that associates with BARD1 to form a RING/RING heterodimer. The BRCA1/BARD1 RING complex functions as an ubiquitin (Ub) ligase with activity substantially greater than individual BRCA1 or BARD1 subunits. By using NMR spectroscopy and site-directed mutagenesis, we have mapped the binding site on the BRCA1/BARD1 heterodimer for the Ub-conjugating enzyme UbcH5c. The results demonstrate that UbcH5c binds only to the BRCA1 RING domain and not the BARD1 RING. The binding interface is formed by the first and second Zn2+-loops and central α-helix of the BRCA1 RING domain, a region disrupted by cancer-predisposing mutations. Unexpectedly, a second Ub-conjugating enzyme, UbcH7, also interacts with the BRCA1/BARD1 complex with similar affinity, although it is not active in Ub-ligase activity assays. Thus, binding alone is not sufficient for BRCA1-dependent Ub-ligase activity.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=156255Documentos Relacionados
- Identification of an SCF ubiquitin–ligase complex required for auxin response in Arabidopsis thaliana
- Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains
- The SCFCOI1 Ubiquitin-Ligase Complexes Are Required for Jasmonate Response in Arabidopsis
- Degradation of the Transcription Factor Gcn4 Requires the Kinase Pho85 and the SCFCDC4 Ubiquitin–Ligase Complex
- Covalent modifier NEDD8 is essential for SCF ubiquitin-ligase in fission yeast