5EN2

Molecular basis for antibody-mediated neutralization of New World hemorrhagic fever mammarenaviruses

Summary for 5EN2

• Entry DOI: 10.2210/pdb5en2/pdb
• Descriptor: GD01 heavy chain, GD01 light chain, Pre-glycoprotein polyprotein GP complex, ... (8 entities in total)
• Functional Keywords: immunoglobulin, glycoprotein, virus, complex, viral protein-immune system complex, viral protein/immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 65855.84

Authors

Mahmutovic, S.,Clark, L.,Levis, S.,Briggiler, A.,Enria, D.,Harrison, S.C.,Abraham, J. (deposition date: 2015-11-09, release date: 2015-12-30, Last modification date: 2024-11-20)

Primary citation

Mahmutovic, S.,Clark, L.,Levis, S.C.,Briggiler, A.M.,Enria, D.A.,Harrison, S.C.,Abraham, J.
Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses.
Cell Host Microbe, 18:705-713, 2015

PubMed Abstract: In the Western hemisphere, at least five mammarenaviruses cause human viral hemorrhagic fevers with high case fatality rates. Junín virus (JUNV) is the only hemorrhagic fever virus for which transfusion of survivor immune plasma that contains neutralizing antibodies ("passive immunity") is an established treatment. Here, we report the structure of the JUNV surface glycoprotein receptor-binding subunit (GP1) bound to a neutralizing monoclonal antibody. The antibody engages the GP1 site that binds transferrin receptor 1 (TfR1)-the host cell surface receptor for all New World hemorrhagic fever mammarenaviruses-and mimics an important receptor contact. We show that survivor immune plasma contains antibodies that bind the same epitope. We propose that viral receptor-binding site accessibility explains the success of passive immunity against JUNV and that this functionally conserved epitope is a potential target for therapeutics and vaccines to limit infection by all New World hemorrhagic fever mammarenaviruses.

PubMed: 26651946
DOI: 10.1016/j.chom.2015.11.005

Experimental method

X-RAY DIFFRACTION (1.821 Å)