5C6T: Crystal structure of HCMV glycoprotein B in complex with 1G2 Fab

Citation:
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.
PDB ID: 5C6TDownload
MMDB ID: 132948
PDB Deposition Date: 2015/6/23
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 3.6  Å
Source Organism:
Human herpesvirus 5 strain Towne
Similar Structures:
Biological Unit for 5C6T: nonameric; determined by author and by software (PISA)
Molecular Components in 5C6T
Label Count Molecule
Proteins (9 molecules)
3
Envelope Glycoprotein B
Molecule annotation
3
1G2 FAB Heavy Chain
Molecule annotation
3
1G2 FAB Light Chain
Molecule annotation
Chemicals (33 molecules)
1
30
2
3
* Click molecule labels to explore molecular sequence information.

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