Mutational analyses of Epstein-Barr virus glycoprotein 42 reveal functional domains not involved in receptor binding but required for membrane fusion.
Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with malignancies of both epithelial and lymphoid origin. Efficient infection of the latent host reservoir B lymphocytes involves the binding of glycoproteins gp350/220 for initial attachment, followed by the concerted action of gH, gL, gB, and gp42 for membrane fusion. The type II membrane protein gp42 is required for infection of B cells and assembles into a complex with gH and gL. The cellular host receptor for gp42, class II human leukocyte antigen (HLA), has been structurally verified by crystallization analyses of gp42 bound to HLA-DR1. Interestingly, the crystal structure revealed a hydrophobic pocket consisting of many aromatic and aliphatic residues from the predicted C-type lectin domain of gp42 that in other members of the C-type lectin family binds major histocompatibility complex class I or other diverse ligands. Although the hydrophobic pocket does not bind HLA class II, mutational analyses presented here indicate that this domain is essential for EBV-induced membrane fusion. In addition, mutational analysis of the region of gp42 contacting HLA class II in the gp42-HLA-DR1 cocrystal confirms that this region interacts with HLA class II and that this interaction is also important for EBV-induced membrane fusion.
Silva
Amanda L
AL
Department of Microbiology and Immunology, Northwestern University Medical School, Ward 6-231, Chicago, IL 60611, USA.
Omerovic
Jasmina
J
Jardetzky
Theodore S
TS
Longnecker
Richard
R
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D006023:Glycoproteins / Q000737:chemistry* / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000378:metabolism; D008561:Membrane Fusion; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry* / Q000502:physiology
D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D011991:Receptors, Virus; D014764:Viral Proteins