5c6t
Crystal structure of HCMV glycoprotein B in complex with 1G2 Fab
Structural highlights
FunctionGB_HCMVT Envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells. May be involved in the initial attachment via binding to heparan sulfate together with the gM/gN complex that binds heparin with higher affinity. Interacts with host integrin ITGB1, PDGFRA and EGFR that likely serve as postattachment entry receptors. Participates also in the fusion of viral and cellular 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 (By similarity). Viral ligand for CD209/DC-SIGN. This interaction allows capture of viral particles by dendritic (DCs) cells and subsequent virus transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. CMV subverts the migration properties of dendritic cells to gain access to target organs or susceptible cells. Publication Abstract from PubMedHuman cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals and neonates infected in utero. Glycoprotein B (gB), the herpesvirus fusion protein, is a target for neutralizing antibodies and a vaccine candidate due to its indispensable role in infection. Here we show the crystal structure of the HCMV gB ectodomain bound to the Fab fragment of 1G2, a neutralizing human monoclonal antibody isolated from a seropositive subject. The gB/1G2 interaction is dominated by aromatic residues in the 1G2 heavy chain CDR3 protruding into a hydrophobic cleft in the gB antigenic domain 5 (AD-5). Structural analysis and comparison with HSV gB suggest the location of additional neutralizing antibody binding sites on HCMV gB. Finally, immunoprecipitation experiments reveal that 1G2 can bind to HCMV virion gB suggesting that its epitope is exposed and accessible on the virus surface. Our data will support the development of vaccines and therapeutic antibodies against HCMV infection. Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody.,Chandramouli S, Ciferri C, Nikitin PA, Calo S, Gerrein R, Balabanis K, Monroe J, Hebner C, Lilja AE, Settembre EC, Carfi A Nat Commun. 2015 Sep 14;6:8176. doi: 10.1038/ncomms9176. PMID:26365435[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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