5WNB

Structure of antibody 3D3 bound to the linear epitope of RSV G

Summary for 5WNB

• Entry DOI: 10.2210/pdb5wnb/pdb
• Descriptor: mAb 3D3 Fab heavy chain, mAb 3D3 Fab light chain, Major surface glycoprotein G, ... (6 entities in total)
• Functional Keywords: rsv, glycoprotein, g glycoprotein, viral protein, viral attachment protein, antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Cellular location: Virion membrane . Isoform Secreted glycoprotein G: Secreted: P03423
• Total number of polymer chains: 6
• Total formula weight: 100364.62

Authors

Fedechkin, S.O.,George, N.L.,Wolff, J.T.,Kauvar, L.M.,DuBois, R.M. (deposition date: 2017-07-31, release date: 2018-03-14, Last modification date: 2024-10-09)

Primary citation

Fedechkin, S.O.,George, N.L.,Wolff, J.T.,Kauvar, L.M.,DuBois, R.M.
Structures of respiratory syncytial virus G antigen bound to broadly neutralizing antibodies.
Sci Immunol, 3:-, 2018

PubMed Abstract: Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in young children and the elderly. The viral envelope G glycoprotein contributes to pathogenesis through its roles in host cell attachment and modulation of host immunity. Although the G glycoprotein is a target of protective RSV-neutralizing antibodies, its development as a vaccine antigen has been hindered by its heterogeneous glycosylation and sequence variability outside a conserved central domain (CCD). We describe the cocrystal structures of two high-affinity broadly neutralizing human monoclonal antibodies bound to the RSV G CCD. The antibodies bind to neighboring conformational epitopes, which we named antigenic sites γ1 and γ2, that span a highly conserved surface, illuminating an important region of vulnerability. We further show that isolated RSV G CCD activates the chemokine receptor CX3CR1 and that antibodies block this activity. These studies provide a template for rational vaccine design targeting this key contributor to RSV disease.

PubMed: 29523582
DOI: 10.1126/sciimmunol.aar3534

Experimental method

X-RAY DIFFRACTION (2.4 Å)