The cytosolic tail of class I MHC heavy chain is required for its dislocation by the human cytomegalovirus US2 and US11 gene products.
The US2 and US11 glycoproteins of human cytomegalovirus facilitate destruction of MHC class I heavy chains by proteasomal proteolysis through acceleration of endoplasmic reticulum-to-cytosol dislocation. Modification of the class I heavy chain was used to probe the structural requirements for this sequence of reactions. The cytosolic domain of the class I heavy chain is required for dislocation to the cytosol and for its subsequent destruction. However, interactions between US2 or US11 and the heavy chain are maintained in the absence of the class I cytosolic domain, as shown by chemical crosslinking in vivo and coprecipitation when translated in vitro. Thus, substrate recognition and accelerated destruction of the heavy chain, as facilitated by US2 or US11, are separable events.
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
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Ploegh
D001254:Astrocytoma / Q000378:metabolism; D002460:Cell Line; D003432:Cross-Linking Reagents; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003587:Cytomegalovirus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D013388:Succinimides; D014162:Transfection; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D003432:Cross-Linking Reagents; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D013388:Succinimides; C074546:US11 protein, herpesvirus; C118670:US2 protein, Varicellovirus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C011240:dithiobis(succinimidylpropionate)