Different HECT domain ubiquitin ligases employ distinct mechanisms of polyubiquitin chain synthesis

  • Wang M
  • Pickart C
  • 55


    Mendeley users who have this article in their library.
  • 72


    Citations of this article.


Individual ubiquitin (Ub)-protein ligases (E3s) cooperate with specific Ub-conjugating enzymes (E2s) to modify cognate substrates with polyubiquitin chains. E3s belonging to the Really Interesting New Gene (RING) and Homologous to E6-Associated Protein (E6AP) C-Terminus (HECT) domain families utilize distinct molecular mechanisms. In particular, HECT E3s, but not RING E3s, form a thiol ester with Ub before transferring Ub to the substrate lysine. Here we report that different HECT domain E3s can employ distinct mechanisms of polyubiquitin chain synthesis. We show that E6AP builds up a K48-linked chain on its HECT cysteine residue, while KIAA10 builds up K48- and K29-linked chains as free entities. A small region near the N-terminus of the conserved HECT domain helps to bring about this functional distinction. Thus, a given HECT domain can specify both the linkage of a polyubiquitin chain and the mechanism of its assembly.

Author-supplied keywords

  • Conjugation
  • HECT domain
  • Polyubiquitin
  • Ubiquitin
  • Ubiquitin ligase

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text


  • Min Wang

  • Cecile M. Pickart

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free