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The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2.

Ubiquitin chains of different topologies trigger distinct functional consequences, including protein degradation and reorganization of complexes. The assembly of most ubiquitin chains is promoted by E2s, yet how these enzymes achieve linkage specificity is poorly understood. We have discovered that the K11-specific Ube2S orients the donor ubiquitin through an essential noncovalent interaction that occurs in addition to the thioester bond at the E2 active site. The E2-donor ubiquitin complex transiently recognizes the acceptor ubiquitin, primarily through electrostatic interactions. The recognition of the acceptor ubiquitin surface around Lys11, but not around other lysines, generates a catalytically competent active site, which is composed of residues of both Ube2S and ubiquitin. Our studies suggest that monomeric E2s promote linkage-specific ubiquitin chain formation through substrate-assisted catalysis.

Pubmed ID: 21376237


  • Wickliffe KE
  • Lorenz S
  • Wemmer DE
  • Kuriyan J
  • Rape M



Publication Data

March 4, 2011

Associated Grants

  • Agency: NIH HHS, Id: DP2 OD003088
  • Agency: NIH HHS, Id: DP2 OD003088-01
  • Agency: NIGMS NIH HHS, Id: GM68933
  • Agency: NIGMS NIH HHS, Id: GM83064
  • Agency: NIGMS NIH HHS, Id: NIH-GM 68933
  • Agency: NIGMS NIH HHS, Id: R01 GM083064
  • Agency: NIGMS NIH HHS, Id: R01 GM083064-03
  • Agency: NCRR NIH HHS, Id: RR15756

Mesh Terms

  • Catalysis
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Ubiquitin
  • Ubiquitin-Conjugating Enzymes