Structural and functional insights to ubiquitin-like protein conjugation

Annu Rev Biophys. 2014;43:357-79. doi: 10.1146/annurev-biophys-051013-022958.

Abstract

Attachment of ubiquitin (Ub) and ubiquitin-like proteins (Ubls) to cellular proteins regulates numerous cellular processes including transcription, the cell cycle, stress responses, DNA repair, apoptosis, immune responses, and autophagy, to name a few. The mechanistically parallel but functionally distinct conjugation pathways typically require the concerted activities of three types of protein: E1 Ubl-activating enzymes, E2 Ubl carrier proteins, and E3 Ubl ligases. E1 enzymes initiate pathway specificity for each cascade by recognizing and activating cognate Ubls, followed by catalyzing Ubl transfer to cognate E2 protein(s). Under certain circumstances, the E2 Ubl complex can direct ligation to the target protein, but most often requires the cooperative activity of E3 ligases. Reviewed here are recent structural and functional studies that improve our mechanistic understanding of E1-, E2-, and E3-mediated Ubl conjugation.

Keywords: E1; E2; E3; ligase; ubiquitin; ubiquitin-like protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Protein Processing, Post-Translational*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination*
  • Ubiquitins / chemistry
  • Ubiquitins / metabolism

Substances

  • Ubiquitins
  • Ubiquitin-Protein Ligases