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TitleMolecular organization of the New World arenavirus spike glycoprotein complex.
Journal, issue, pagesNat Microbiol, Vol. 10, Issue 9, Page 2207-2220, Year 2025
Publish dateAug 8, 2025
AuthorsColin J Mann / Pan Yang / Daniel Olal / Xiaoyi Fan / Katherine Nabel Smith / Lars E Clark / Florian Krammer / Yuemin Bian / Jonathan Abraham /
PubMed AbstractOf 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 ...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.
External linksNat Microbiol / PubMed:40781447 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.0 Å
Structure data

48598

9mt2

EMDB-48598, PDB-9mt2:
Structure of the Machupo virus glycoprotein complex
Method: EM (single particle) / Resolution: 2.9 Å

48601

9mt6

EMDB-48601, PDB-9mt6:
Structure of the Junin virus glycoprotein complex
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-ZN:
Unknown entry

Source
  • mammarenavirus machupoense
  • mammarenavirus juninense
KeywordsVIRAL PROTEIN / Fusogen / glycoprotein / Complex / membrane

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