A UbcH5/ubiquitin noncovalent complex is required for processive BRCA1-directed ubiquitination.

Abstract

Protein ubiquitination is a powerful regulatory modification that influences nearly every aspect of eukaryotic cell biology. The general pathway for ubiquitin (Ub) modification requires the sequential activities of a Ub-activating enzyme (E1), a Ub transfer enzyme (E2), and a Ub ligase (E3). The E2 must recognize both the E1 and a cognate E3 in addition to carrying activated Ub. These central functions are performed by a topologically conserved alpha/beta-fold core domain of approximately 150 residues shared by all E2s. However, as presented herein, the UbcH5 family of E2s can also bind Ub noncovalently on a surface well removed from the E2 active site. We present the solution structure of the UbcH5c/Ub noncovalent complex and demonstrate that this noncovalent interaction permits self-assembly of activated UbcH5c approximately Ub molecules. Self-assembly has profound consequences for the processive formation of polyubiquitin (poly-Ub) chains in ubiquitination reactions directed by the breast and ovarian cancer tumor susceptibility protein BRCA1.

• Authors: Peter S Brzovic, Alexei Lissounov, Devin E Christensen, David W Hoyt, Rachel E Klevit
• Journal: Molecular cell (Mol Cell) Vol. 21 Issue 6 Pg. 873-80 (Mar 17 2006) ISSN: 1097-2765 [Print] United States
• PMID: 16543155 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• BRCA1 Protein
• Ubiquitin
• Polyubiquitin
• Ubiquitin-Conjugating Enzymes
• Ubiquitin-Protein Ligases

Topics

• Amino Acid Sequence
• BRCA1 Protein (metabolism)
• Magnetic Resonance Spectroscopy
• Models, Biological
• Molecular Sequence Data
• Polyubiquitin (metabolism)
• Protein Binding
• Protein Structure, Tertiary
• Sequence Homology, Amino Acid
• Ubiquitin (chemistry, metabolism, physiology)
• Ubiquitin-Conjugating Enzymes (chemistry, metabolism)
• Ubiquitin-Protein Ligases