title: Human herpesvirus 7 U21 tetramerizes to associate with class I major histocompatibility complex molecules.
abstract: The U21 gene product from human herpesvirus 7 binds to and redirects class I major histocompatibility complex (MHC) molecules to a lysosomal compartment. The molecular mechanism by which U21 reroutes class I MHC molecules to lysosomes is not known. Here, we have reconstituted the interaction between purified soluble U21 and class I MHC molecules, suggesting that U21 does not require additional cellular proteins to interact with class I MHC molecules. Our results demonstrate that U21, itself predicted to contain an MHC class I-like protein fold, interacts tightly with class I MHC molecules as a tetramer, in a 4:2 stoichiometry. These observations have helped to elucidate a refined model describing the mechanism by which U21 escorts class I MHC molecules to the lysosomal compartment.
  
  
  OBJECTIVE
  In this report, we show that the human herpesvirus 7 (HHV-7) immunoevasin U21, itself a class I MHC-like protein, binds with high affinity to class I MHC molecules as a tetramer and escorts them to lysosomes, where they are degraded. While many class I MHC-like molecules have been described in detail, this unusual viral class I-like protein functions as a tetramer, associating with class I MHC molecules in a 4:2 ratio, illuminating a functional significance of homooligomerization of a class I MHC-like protein.
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: May
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Wang
authors.forename: Andrea
authors.initials: A
authors.lastname: Balbo
authors.forename: Sheryl L
authors.initials: SL
authors.lastname: Konrad
authors.forename: Rico
authors.initials: R
authors.lastname: Buchli
authors.forename: William H
authors.initials: WH
authors.lastname: Hildebrand
authors.forename: Peter
authors.initials: P
authors.lastname: Schuck
authors.forename: Amy W
authors.initials: AW
authors.lastname: Hudson
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016199:Herpesvirus 7, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D055503:Protein Multimerization; D019349:Roseolovirus Infections / Q000378:metabolism* / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; C488324:U21 glycoprotein, human herpesvirus 7; D014764:Viral Proteins