6C5V
An anti-gH/gL antibody that neutralizes dual-tropic infection defines a site of vulnerability on Epstein-Barr virus
Summary for 6C5V
| Entry DOI | 10.2210/pdb6c5v/pdb |
| EMDB information | 7344 7345 |
| Descriptor | Envelope glycoprotein H, Envelope glycoprotein L, Glycoprotein 42, ... (7 entities in total) |
| Functional Keywords | epstein-barr virus, neutralizing antibodies, gh/gl, glycoproteins, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein |
| Biological source | Human herpesvirus 4 (HHV-4) More |
| Total number of polymer chains | 5 |
| Total formula weight | 167514.83 |
| Authors | Snijder, J.,Ortego, M.S.,Weidle, C.,Stuart, A.B.,Gray, M.A.,McElrath, M.J.,Pancera, M.,Veesler, D.,McGuire, A.T.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2018-01-16, release date: 2018-05-02, Last modification date: 2020-07-29) |
| Primary citation | Snijder, J.,Ortego, M.S.,Weidle, C.,Stuart, A.B.,Gray, M.D.,McElrath, M.J.,Pancera, M.,Veesler, D.,McGuire, A.T. An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus. Immunity, 48:799-811.e9, 2018 Cited by PubMed Abstract: Epstein-Barr virus (EBV) is a causative agent of infectious mononucleosis and is associated with 200,000 new cases of cancer and 140,000 deaths annually. Subunit vaccines against this pathogen have focused on the gp350 glycoprotein and remain unsuccessful. We isolated human antibodies recognizing the EBV fusion machinery (gH/gL and gB) from rare memory B cells. One anti-gH/gL antibody, AMMO1, potently neutralized infection of B cells and epithelial cells, the two major cell types targeted by EBV. We determined a cryo-electron microscopy reconstruction of the gH/gL-gp42-AMMO1 complex and demonstrated that AMMO1 bound to a discontinuous epitope formed by both gH and gL at the Domain-I/Domain-II interface. Integrating structural, biochemical, and infectivity data, we propose that AMMO1 inhibits fusion of the viral and cellular membranes. This work identifies a crucial epitope that may aid in the design of next-generation subunit vaccines against this major public health burden. PubMed: 29669253DOI: 10.1016/j.immuni.2018.03.026 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.8 Å) |
Structure validation
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