5C6T

Crystal structure of HCMV glycoprotein B in complex with 1G2 Fab

Summary for 5C6T

• Entry DOI: 10.2210/pdb5c6t/pdb
• Descriptor: Envelope glycoprotein B, 1G2 Fab heavy chain, 1G2 Fab light chain, ... (6 entities in total)
• Functional Keywords: cytomegalovirus, glycoprotein b, gb, 1g2, complex, viral protein-immue system complex, viral protein/immue system
• Biological source: Human cytomegalovirus (HHV-5); More
• Cellular location: Virion membrane ; Single-pass type I membrane protein : P13201
• Total number of polymer chains: 3
• Total formula weight: 123408.09

Authors

Chandramouli, S.,Ciferri, C.,Settembre, E.C.,Carfi, A. (deposition date: 2015-06-23, release date: 2015-09-23, Last modification date: 2024-11-06)

Primary citation

Chandramouli, S.,Ciferri, C.,Nikitin, P.A.,Calo, S.,Gerrein, R.,Balabanis, K.,Monroe, J.,Hebner, C.,Lilja, A.E.,Settembre, E.C.,Carfi, A.
Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody.
Nat Commun, 6:8176-8176, 2015

PubMed Abstract: Human 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.

PubMed: 26365435
DOI: 10.1038/ncomms9176

Experimental method

X-RAY DIFFRACTION (3.6 Å)