8tnn

Crystal structure of Epstein-Barr virus gH/gL/gp42 in complex with gp42 antibody A10

spinqualitylabelsall models 8tnn, resolution 3.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8tnn is a 10 chain structure with sequence from Human herpesvirus 4 strain B95-8 and Macaca fascicularis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.36Å Ligands: BMA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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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