8DMH

Lymphocytic choriomeningitis virus glycoprotein in complex with neutralizing antibody M28

Summary for 8DMH

• Entry DOI: 10.2210/pdb8dmh/pdb
• EMDB information: 27538
• Descriptor: Glycoprotein G1, 18.5C-M28 Fab Light Chain, 18.5C-M28 Fab Heavy Chain, ... (7 entities in total)
• Functional Keywords: viral glycoprotein, arenavirus, lcmv, gp, antibody, neutralization, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Lymphocytic choriomeningitis virus; More
• Total number of polymer chains: 12
• Total formula weight: 353269.35

Authors

Moon-Walker, A.,Hastie, K.M.,Zyla, D.S.,Saphire, E.O. (deposition date: 2022-07-08, release date: 2023-04-12, Last modification date: 2024-10-23)

Primary citation

Moon-Walker, A.,Zhang, Z.,Zyla, D.S.,Buck, T.K.,Li, H.,Diaz Avalos, R.,Schendel, S.L.,Hastie, K.M.,Crotty, S.,Saphire, E.O.
Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus.
Cell Chem Biol, 30:403-411.e4, 2023

PubMed Abstract: The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if acquired during pregnancy. The structure of the trimeric surface glycoprotein, essential for entry, vaccine design, and antibody neutralization, remains unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of the LCMV surface glycoprotein (GP) in its trimeric pre-fusion assembly both alone and in complex with a rationally engineered monoclonal neutralizing antibody termed 18.5C-M28 (M28). Additionally, we show that passive administration of M28, either as a prophylactic or therapeutic, protects mice from LCMV clone 13 (LCMV) challenge. Our study illuminates not only the overall structural organization of LCMV GP and the mechanism for its inhibition by M28 but also presents a promising therapeutic candidate to prevent severe or fatal disease in individuals who are at risk of infection by a virus that poses a threat worldwide.

PubMed: 36990092
DOI: 10.1016/j.chembiol.2023.03.005

Experimental method

ELECTRON MICROSCOPY (3.19 Å)