title: Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II receptor HLA-DR1.
abstract: Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.
authors.affiliation: Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Mullen
authors.forename: Keith M
authors.initials: KM
authors.lastname: Haan
authors.forename: Richard
authors.initials: R
authors.lastname: Longnecker
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Jardetzky
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000737:chemistry* / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D037102:Lectins; D008561:Membrane Fusion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: C101688:BZLF2 protein, Herpesvirus 4, Human; D006023:Glycoproteins; D015798:HLA-DR1 Antigen; D037102:Lectins; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins