9CQB

Antibody 1G8 bound to the central conserved domain of RSV G

Summary for 9CQB

• Entry DOI: 10.2210/pdb9cqb/pdb
• Descriptor: Fab 1G8 Light Chain, Fab 1G8 Heavy Chain, Mature secreted glycoprotein G, ... (4 entities in total)
• Functional Keywords: antibody, respiratory syncytial virus, g glycoprotein, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 57274.96

Authors

Juarez, M.J.,DuBois, M.J. (deposition date: 2024-07-19, release date: 2025-02-19, Last modification date: 2025-04-02)

Primary citation

Juarez, M.G.,O'Rourke, S.M.,Dzimianski, J.V.,Gagnon, D.,Penunuri, G.,Serrao, V.H.B.,Corbett-Detig, R.B.,Kauvar, L.M.,DuBois, R.M.
Structures of respiratory syncytial virus G bound to broadly reactive antibodies provide insights into vaccine design.
Sci Rep, 15:8666-8666, 2025

PubMed Abstract: Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease in infants and older adults. The attachment glycoprotein (RSV G) binds to the chemokine receptor CX3CR1 to promote viral entry and modulate host immunity. Antibodies against RSV G are a known correlate of protection. Previously, several broadly reactive, high-affinity anti-RSV G human monoclonal antibodies were isolated from RSV-exposed individuals and were shown to be protective in vitro and in vivo. Here, we determined the structures of three of these antibodies in complex with RSV G and defined distinct conformational epitopes comprised of highly conserved RSV G residues. Binding competition and structural studies demonstrated that this highly conserved region displays two non-overlapping antigenic sites. Analyses of anti-RSV G antibody sequences reveal that antigenic site flexibility may promote the elicitation of diverse antibody germlines. Together, these findings provide a foundation for next-generation RSV prophylactics, and they expand concepts in vaccine design for the elicitation of germline lineage-diverse, broadly reactive, high-affinity antibodies.

PubMed: 40082629
DOI: 10.1038/s41598-025-92886-w

Experimental method

X-RAY DIFFRACTION (2.5 Å)