A novel polyubiquitin chain linkage formed by viral Ubiquitin is resistant to host deubiquitinating enzymes

Biochem J. 2020 Jun 26;477(12):2193-2219. doi: 10.1042/BCJ20200289.

Abstract

The Baculoviridae family of viruses encode a viral Ubiquitin (vUb) gene. Though the vUb is homologous to the host eukaryotic Ubiquitin (Ub), its preservation in the viral genome indicates unique functions that are not compensated by the host Ub. We report the structural, biophysical, and biochemical properties of the vUb from Autographa californica multiple nucleo-polyhedrosis virus (AcMNPV). The packing of central helix α1 to the beta-sheet β1-β5 is different between vUb and Ub. Consequently, its stability is lower compared with Ub. However, the surface properties, ubiquitination activity, and the interaction with Ubiquitin-binding domains are similar between vUb and Ub. Interestingly, vUb forms atypical polyubiquitin chain linked by lysine at the 54th position (K54), and the deubiquitinating enzymes are ineffective against the K54-linked polyubiquitin chains. We propose that the modification of host/viral proteins with the K54-linked chains is an effective way selected by the virus to protect the vUb signal from host DeUbiquitinases.

Keywords: NMR spectroscopy; Ubiquitins; host–pathogen interactions; post-translational modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Closterovirus / metabolism*
  • Deubiquitinating Enzymes / chemistry
  • Deubiquitinating Enzymes / genetics
  • Deubiquitinating Enzymes / metabolism*
  • HEK293 Cells
  • Humans
  • Lysine / chemistry
  • Lysine / genetics
  • Lysine / metabolism
  • Polyubiquitin / chemistry
  • Polyubiquitin / metabolism*
  • Protein Conformation
  • Protein Processing, Post-Translational*
  • Saccharomyces cerevisiae / metabolism*
  • Sequence Homology
  • Ubiquitination*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism*

Substances

  • Viral Proteins
  • Polyubiquitin
  • Deubiquitinating Enzymes
  • Lysine