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Title: 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 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

Authors:
; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
881096
Report Number(s):
PNNL-SA-48810
2612d; 2447a; 2034a; 2612c; 2612b; 2612a; KP1704020; TRN: US200623%%609
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Molecular Cell, 21(6):873-880
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; BIOLOGY; ENZYMES; LIGASES; MAMMARY GLANDS; MODIFICATIONS; NEOPLASMS; PROTEINS; RESIDUES; Environmental Molecular Sciences Laboratory

Citation Formats

Brzovic, Peter S., Lissounov, Alexei V., Christensen, Devin, Hoyt, David W., and Klevit, Rachel E.. A UbcH5/Ubiquitin Noncovalent Complex is Required for Processive BRCA1-Directed Ubiquitination. United States: N. p., 2006. Web. doi:10.1016/j.molcel.2006.02.008.
Brzovic, Peter S., Lissounov, Alexei V., Christensen, Devin, Hoyt, David W., & Klevit, Rachel E.. A UbcH5/Ubiquitin Noncovalent Complex is Required for Processive BRCA1-Directed Ubiquitination. United States. doi:10.1016/j.molcel.2006.02.008.
Brzovic, Peter S., Lissounov, Alexei V., Christensen, Devin, Hoyt, David W., and Klevit, Rachel E.. Fri . "A UbcH5/Ubiquitin Noncovalent Complex is Required for Processive BRCA1-Directed Ubiquitination". United States. doi:10.1016/j.molcel.2006.02.008.
@article{osti_881096,
title = {A UbcH5/Ubiquitin Noncovalent Complex is Required for Processive BRCA1-Directed Ubiquitination},
author = {Brzovic, Peter S. and Lissounov, Alexei V. and Christensen, Devin and Hoyt, David W. and Klevit, Rachel E.},
abstractNote = {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},
doi = {10.1016/j.molcel.2006.02.008},
journal = {Molecular Cell, 21(6):873-880},
number = ,
volume = ,
place = {United States},
year = {Fri Mar 17 00:00:00 EST 2006},
month = {Fri Mar 17 00:00:00 EST 2006}
}