MHC class I ubiquitination by a viral PHD/LAP finger protein.
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.
Boname
J M
JM
Department of Pathology, Division of Virology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
Stevenson
P G
PG
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018142:Gammaherpesvirinae / Q000235:genetics / Q000472:pathogenicity*; D006183:H-2 Antigens / Q000737:chemistry / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000502:physiology; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D015853:Cysteine Proteinase Inhibitors; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D009097:Multienzyme Complexes; D025801:Ubiquitin; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex