8AHN

Sin Nombre virus Gn in complex with Fab SNV-42

Summary for 8AHN

• Entry DOI: 10.2210/pdb8ahn/pdb
• Descriptor: Envelope polyprotein, Fab SNV-42 light chain, Fab SNV-42 heavy chain, ... (6 entities in total)
• Functional Keywords: sin nombre, virus, hantavirus, fab, snv-42, complex, viral protein
• Biological source: Sin Nombre orthohantavirus; More
• Total number of polymer chains: 3
• Total formula weight: 86480.43

Authors

Stass, R.,Bowden, T.A. (deposition date: 2022-07-22, release date: 2023-05-24, Last modification date: 2024-11-13)

Primary citation

Stass, R.,Engdahl, T.B.,Chapman, N.S.,Wolters, R.M.,Handal, L.S.,Diaz, S.M.,Crowe Jr., J.E.,Bowden, T.A.
Mechanistic basis for potent neutralization of Sin Nombre hantavirus by a human monoclonal antibody.
Nat Microbiol, 8:1293-1303, 2023

PubMed Abstract: Rodent-borne hantaviruses are prevalent worldwide and upon spillover to human populations, cause severe disease for which no specific treatment is available. A potent antibody response is key for recovery from hantavirus infection. Here we study a highly neutralizing human monoclonal antibody, termed SNV-42, which was derived from a memory B cell isolated from an individual with previous Sin Nombre virus (SNV) infection. Crystallographic analysis demonstrates that SNV-42 targets the Gn subcomponent of the tetrameric (Gn-Gc) glycoprotein assembly that is relevant for viral entry. Integration of our 1.8 Å structure with the (Gn-Gc) ultrastructure arrangement indicates that SNV-42 targets the membrane-distal region of the virus envelope. Comparison of the SNV-42 paratope encoding variable genes with inferred germline gene segments reveals high sequence conservation, suggesting that germline-encoded antibodies inhibit SNV. Furthermore, mechanistic assays reveal that SNV-42 interferes with both receptor recognition and fusion during host-cell entry. This work provides a molecular-level blueprint for understanding the human neutralizing antibody response to hantavirus infection.

PubMed: 37322112
DOI: 10.1038/s41564-023-01413-y

Experimental method

X-RAY DIFFRACTION (1.8 Å)