5W1K

JUNV GP1 CR1-10 Fab CR1-28 Fab complex

Summary for 5W1K

• Entry DOI: 10.2210/pdb5w1k/pdb
• Related: 5W1G 5W1M
• Descriptor: CR1-28 Fab light chain, CR1-28 Fab heavy chain, CR1-10 Fab light chain, ... (8 entities in total)
• Functional Keywords: fab, antibody, junin virus, arenavirus, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 20
• Total formula weight: 443009.39

Authors

Raymond, D.D.,Clark, L.E.,Abraham, J. (deposition date: 2017-06-03, release date: 2018-05-30, Last modification date: 2024-10-30)

Primary citation

Clark, L.E.,Mahmutovic, S.,Raymond, D.D.,Dilanyan, T.,Koma, T.,Manning, J.T.,Shankar, S.,Levis, S.C.,Briggiler, A.M.,Enria, D.A.,Wucherpfennig, K.W.,Paessler, S.,Abraham, J.
Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses.
Nat Commun, 9:1884-1884, 2018

PubMed Abstract: While five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1-Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern.

PubMed: 29760382
DOI: 10.1038/s41467-018-04271-z

Experimental method

X-RAY DIFFRACTION (3.99 Å)