MHC class I ubiquitination by a viral PHD/LAP finger protein

Immunity. 2001 Oct;15(4):627-36. doi: 10.1016/s1074-7613(01)00213-8.


The murine gamma-herpesvirus-68 K3 (MK3) is a PHD/LAP finger protein that downregulates major histocompatibility complex (MHC) class I expression. In transfected cell lines, MK3 was expressed in the endoplasmic reticulum (ER) membrane, where it bound the cytoplasmic tail of newly synthesized H-2D(b) glycoproteins and targeted them for degradation. Proteasome inhibitors blocked the degradation and led to an accumulation of ubiquitinated H-2D(b). Because this retained its native conformation, ubiquitination preceded any denaturation or dislocation to the cytosol. The PHD/LAP finger of MK3 was not required for H-2D(b) binding but was essential for its ubiquitination and degradation. Thus, gamma-herpesviruses have adapted the cellular PHD/LAP motif to immune evasion, apparently for the catalysis of MHC class I ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Cysteine Endopeptidases / physiology
  • Cysteine Proteinase Inhibitors / pharmacology
  • Down-Regulation
  • Endoplasmic Reticulum / metabolism
  • Gammaherpesvirinae / genetics
  • Gammaherpesvirinae / pathogenicity*
  • H-2 Antigens / chemistry
  • H-2 Antigens / metabolism*
  • Histocompatibility Antigen H-2D
  • Molecular Sequence Data
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / physiology
  • Mutation
  • Proteasome Endopeptidase Complex
  • Protein Folding
  • Protein Structure, Tertiary
  • Transfection
  • Ubiquitin / metabolism*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism
  • Viral Proteins / pharmacology*


  • Cysteine Proteinase Inhibitors
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Multienzyme Complexes
  • Ubiquitin
  • Viral Proteins
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex