%0 Journal Article %1 Gewurz01062001 %A Gewurz, Benjamin E. %A Wang, Evelyn W. %A Tortorella, Domenico %A Schust, Danny J. %A Ploegh, Hidde L. %D 2001 %J Journal of Virology %K myown %N 11 %P 5197-5204 %R 10.1128/JVI.75.11.5197-5204.2001 %T Human Cytomegalovirus US2 Endoplasmic Reticulum-Lumenal Domain Dictates Association with Major Histocompatibility Complex Class I in a Locus-Specific Manner %U http://jvi.asm.org/content/75/11/5197.abstract %V 75 %X The human cytomegalovirus-encoded US2 glycoprotein targets endoplasmic reticulum-resident major histocompatibility complex (MHC) class I heavy chains for rapid degradation by the proteasome. We demonstrate that the endoplasmic reticulum-lumenal domain of US2 allows tight interaction with class I molecules encoded by the HLA-A locus. Recombinant soluble US2 binds properly folded, peptide-containing recombinant HLA-A2 molecules in a peptide sequence-independent manner, consistent with US2's ability to broadly downregulate class I molecules. The physicochemical properties of the US2/MHC class I complex suggest a 1:1 stoichiometry. These results demonstrate that US2 does not require additional cellular proteins to specifically interact with soluble class I molecules. Binding of US2 does not significantly alter the conformation of class I molecules, as a soluble T-cell receptor can simultaneously recognize class I molecules associated with US2. The lumenal domain of US2 can differentiate between the products of distinct class I loci, as US2 binds several HLA-A locus products while being unable to bind recombinant HLA-B7, HLA-B27, HLA-Cw4, or HLA-E. We did not observe interaction between soluble US2 and either recombinant HLA-DR1 or recombinant HLA-DM. The substrate specificity of US2 may help explain the presence in human cytomegalovirus of multiple strategies for downregulation of MHC class I molecules.

@article{Gewurz01062001, abstract = {The human cytomegalovirus-encoded US2 glycoprotein targets endoplasmic reticulum-resident major histocompatibility complex (MHC) class I heavy chains for rapid degradation by the proteasome. We demonstrate that the endoplasmic reticulum-lumenal domain of US2 allows tight interaction with class I molecules encoded by the HLA-A locus. Recombinant soluble US2 binds properly folded, peptide-containing recombinant HLA-A2 molecules in a peptide sequence-independent manner, consistent with US2's ability to broadly downregulate class I molecules. The physicochemical properties of the US2/MHC class I complex suggest a 1:1 stoichiometry. These results demonstrate that US2 does not require additional cellular proteins to specifically interact with soluble class I molecules. Binding of US2 does not significantly alter the conformation of class I molecules, as a soluble T-cell receptor can simultaneously recognize class I molecules associated with US2. The lumenal domain of US2 can differentiate between the products of distinct class I loci, as US2 binds several HLA-A locus products while being unable to bind recombinant HLA-B7, HLA-B27, HLA-Cw4, or HLA-E. We did not observe interaction between soluble US2 and either recombinant HLA-DR1 or recombinant HLA-DM. The substrate specificity of US2 may help explain the presence in human cytomegalovirus of multiple strategies for downregulation of MHC class I molecules.}, added-at = {2016-12-12T21:33:29.000+0100}, author = {Gewurz, Benjamin E. and Wang, Evelyn W. and Tortorella, Domenico and Schust, Danny J. and Ploegh, Hidde L.}, biburl = {https://www.bibsonomy.org/bibtex/242fb1c26d259c2afba10593acb7a5584/bgewurz}, doi = {10.1128/JVI.75.11.5197-5204.2001}, eprint = {http://jvi.asm.org/content/75/11/5197.full.pdf+html}, interhash = {c2803f562183dbe226c7d01ab1cc21dc}, intrahash = {42fb1c26d259c2afba10593acb7a5584}, journal = {Journal of Virology}, keywords = {myown}, number = 11, pages = {5197-5204}, timestamp = {2016-12-12T21:33:29.000+0100}, title = {Human Cytomegalovirus US2 Endoplasmic Reticulum-Lumenal Domain Dictates Association with Major Histocompatibility Complex Class I in a Locus-Specific Manner}, url = {http://jvi.asm.org/content/75/11/5197.abstract}, volume = 75, year = 2001 }