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

Mol Cell. 2006 Mar 17;21(6):873-80. doi: 10.1016/j.molcel.2006.02.008.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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*
  • Ubiquitin / metabolism
  • Ubiquitin / physiology
  • Ubiquitin-Conjugating Enzymes / chemistry*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Protein Ligases

Substances

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

Associated data

  • PDB/2FUH