Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface

Eduardo Bignon (1) , Amelina Albornoz (1) , Pablo Guardado-Calvo (2) , Félix Rey (2) , Nicole Tischler (1)

1 Fundación Ciencia & Vida
2 Virologie Structurale - Structural Virology

The hantavirus envelope glycoproteins Gn and Gc mediate virion assembly and cell entry, with Gc driving fusion of viral and endosomal membranes. Although the X-ray structures and overall arrangement of Gn and Gc on the hantavirus spikes are known, their detailed interactions are not. Here we show that the lateral contacts between spikes are mediated by the same 2-fold contacts observed in Gc crystals at neutral pH, allowing the engineering of disulfide bonds to cross-link spikes. Disrupting the observed dimer interface affects particle assembly and overall spike stability. We further show that the spikes display a temperature-dependent dynamic behavior at neutral pH, alternating between ‘open’ and ‘closed’ forms. We show that the open form exposes the Gc fusion loops but is off-pathway for productive Gc-induced membrane fusion and cell entry. These data also provide crucial new insights for the design of optimized Gn/Gc immunogens to elicit protective immune responses.

Keywords: Bunyavirales order; biochemistry; chemical biology; envelope proteins; infectious disease; inter-spike interface; membrane fusion; microbiology; viral breathing; virus

Domains: Structural Biology [q-bio.BM]

Eduardo Bignon, Amelina Albornoz, Pablo Guardado-Calvo, Félix Rey, Nicole Tischler. Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface. eLife, 2019, 8, pp.e46028. ⟨10.7554/eLife.46028⟩. ⟨pasteur-03207972⟩