9MT6

Structure of the Junin virus glycoprotein complex

Summary for 9MT6

• Entry DOI: 10.2210/pdb9mt6/pdb
• EMDB information: 48601
• Descriptor: JUNV GP1, Pre-glycoprotein polyprotein GP complex, JUNV GP2, ... (6 entities in total)
• Functional Keywords: fusogen, glycoprotein, membrane, complex, viral protein
• Biological source: Mammarenavirus juninense; More
• Total number of polymer chains: 9
• Total formula weight: 172720.36

Authors

Mann, C.J.,Abraham, J. (deposition date: 2025-01-10, release date: 2025-07-16, Last modification date: 2026-02-25)

Primary citation

Mann, C.J.,Yang, P.,Olal, D.,Fan, X.,Smith, K.N.,Clark, L.E.,Krammer, F.,Bian, Y.,Abraham, J.
Molecular organization of the New World arenavirus spike glycoprotein complex.
Nat Microbiol, 10:2207-2220, 2025

PubMed Abstract: Of the multiple arenaviruses that cause haemorrhagic fevers in the Americas, all lack reliable therapeutic options, and only one has a vaccine. The arenavirus glycoprotein complex (GPC) binds cellular receptors and mediates pH-dependent fusion of viral and host cell membranes during entry. GPC comprises GP1, GP2 and stable signal peptide (SSP) subunits. SSP remains associated with the mature glycoprotein complex and regulates pH-dependent membrane fusion through an unclear mechanism. We report cryo-EM structures of Junin virus and Machupo virus GPC stabilized in the prefusion conformation using an amino acid substitution in the transmembrane region of SSP at 3.0 Å and 2.9 Å resolution, respectively. Mutational analyses, cell-cell fusion assays and molecular dynamics simulations reveal how contacts in the membrane-proximal and transmembrane regions of GPC regulate pH-dependent membrane fusion. The structures may aid in the design of therapeutic antibody cocktails, small-molecule inhibitors and vaccines against arenaviruses.

PubMed: 40781447
DOI: 10.1038/s41564-025-02085-6

Experimental method

ELECTRON MICROSCOPY (3 Å)