The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases

Trends Cell Biol. 2000 Oct;10(10):429-39. doi: 10.1016/s0962-8924(00)01834-1.

Abstract

Recently, many new examples of E3 ubiquitin ligases or E3 enzymes have been found to regulate a host of cellular processes. These E3 enzymes direct the formation of multiubiquitin chains on specific protein substrates, and - typically - the subsequent destruction of those proteins. We discuss how the modular architecture of E3 enzymes connects one of two distinct classes of catalytic domains to a wide range of substrate-binding domains. In one catalytic class, a HECT domain transfers ubiquitin directly to substrate bound to a non-catalytic domain. Members of the other catalytic class, found in the SCF, VBC and APC complexes, use a RING finger domain to facilitate ubiquitylation. The separable substrate-recognition domains of E3 enzymes provides a flexible means of linking a conserved ubiquitylation function to potentially thousands of ubiquitylated substrates in eukaryotic cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Catalytic Domain
  • Eukaryotic Cells / enzymology
  • Humans
  • Ligases / chemistry
  • Ligases / metabolism*
  • Substrate Specificity / physiology
  • Ubiquitin-Protein Ligases

Substances

  • Ubiquitin-Protein Ligases
  • Ligases