How USP18 deals with ISG15-modified proteins: structural basis for the specificity of the protease

FEBS J. 2018 Mar;285(6):1024-1029. doi: 10.1111/febs.14260. Epub 2017 Sep 21.

Abstract

The ubiquitin-specific protease 18 (USP18) has two major functions: (a) it is a highly specific protease that cleaves the ubiquitin-like modifier ISG15 (interferon-stimulated gene 15) from proteins, and (b) independent from its enzymatic activity USP18 interacts with the type I interferon receptor and shuts off downstream signaling. The structures of USP18 and a USP18-ISG15 complex revealed the molecular basis of the unique specificity of the protease and might shed some light into its interaction with the interferon receptor.

Keywords: ISG15; USP; cysteine protease; interferon.

Publication types

  • Review

MeSH terms

  • Cytokines / chemistry
  • Cytokines / metabolism*
  • Endopeptidases / chemistry
  • Endopeptidases / metabolism*
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Domains
  • Proteolysis
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction*
  • Substrate Specificity
  • Ubiquitin Thiolesterase
  • Ubiquitins / chemistry
  • Ubiquitins / metabolism*

Substances

  • Cytokines
  • Ubiquitins
  • Receptor, Interferon alpha-beta
  • ISG15 protein, human
  • Endopeptidases
  • USP18 protein, human
  • Ubiquitin Thiolesterase