A UbcH5/Ubiquitin Noncovalent Complex is Required for Processive BRCA1-Directed Ubiquitination

Journal Article · Fri Mar 17 04:00:00 EST 2006 · Molecular Cell, 21(6):873-880

DOI:https://doi.org/10.1016/j.molcel.2006.02.008· OSTI ID:881096

Brzovic, Peter S; Lissounov, Alexei V; Christensen, Devin; Hoyt, David W; Klevit, Rachel E

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 a/b-fold core domain ofw150 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 UbcH5cwUb 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

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 881096
• Report Number(s): PNNL-SA-48810; 2612d; 2447a; 2034a; 2612c; 2612b; 2612a; KP1704020
• Journal Information: Molecular Cell, 21(6):873-880, Journal Name: Molecular Cell, 21(6):873-880
• Country of Publication: United States
• Language: English

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