8tnt

Crystal structure of Epstein-Barr virus gH/gL/gp42 in complex with antibodies F-2-1 and 769C2

spinqualitylabelsall models 8tnt, resolution 3.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8tnt is a 7 chain structure with sequence from Homo sapiens, Human gammaherpesvirus 4 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.15Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GH_EBVB9 The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma membranes leading to virus entry into the host cell. Membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL. Fusion of EBV with B-lymphocytes requires the additional receptor-binding protein gp42, which forms a complex with gH/gL. May also be required for virus attachment to epithelial cells. Publication Abstract from PubMed Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with B cell lymphomas. EBV glycoprotein 42 (gp42) binds HLA class II and activates membrane fusion with B cells. We isolated gp42-specific monoclonal antibodies (mAbs), A10 and 4C12, which use distinct mechanisms to neutralize virus infection. mAb A10 was more potent than the only known neutralizing gp42 mAb, F-2-1, in neutralizing EBV infection and blocking binding to HLA class II. mAb 4C12 was similar to mAb A10 in inhibiting glycoprotein-mediated B cell fusion but did not block receptor binding, and it was less effective in neutralizing infection. Crystallographic structures of gH/gL/gp42/A10 and gp42/4C12 complexes revealed two distinct sites of vulnerability on gp42 for receptor binding and B cell fusion. Passive transfer of mAb A10 into humanized mice conferred nearly 100% protection from viremia and EBV lymphomas after EBV challenge. These findings identify vulnerable sites on EBV that may facilitate therapeutics and vaccines. Epstein-Barr virus gp42 antibodies reveal sites of vulnerability for receptor binding and fusion to B cells.,Bu W, Kumar A, Board NL, Kim J, Dowdell K, Zhang S, Lei Y, Hostal A, Krogmann T, Wang Y, Pittaluga S, Marcotrigiano J, Cohen JI Immunity. 2024 Mar 12;57(3):559-573.e6. doi: 10.1016/j.immuni.2024.02.008. PMID:38479361 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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