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

• Published in: eLife Vol. 8
• Main Authors: Bignon, Eduardo A, Albornoz, Amelina, Guardado-Calvo, Pablo, Rey, Félix A, Tischler, Nicole D
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 10-06-2019; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Amino Acid Sequence; Biochemistry and Chemical Biology; Biochemistry, Molecular Biology; Bunyavirales order; Cell fusion; Crystallography, X-Ray; Crystals; Disulfide bonds; envelope proteins; Fusion protein; Glycoproteins; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - metabolism; Hantavirus; Hantavirus - genetics; Hantavirus - metabolism; Hantavirus - physiology; Hydrogen-Ion Concentration; Immune response; inter-spike interface; Life Sciences; Membrane Fusion; Microbiology and Infectious Disease; Models, Molecular; pH effects; Protein Conformation; Protein Multimerization; Protein Stability; Proteins; Sequence Homology, Amino Acid; Structural Biology; Temperature; viral breathing; Viral Envelope Proteins; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Virions; Virology; Virus Assembly; Virus Internalization; chemical biology; Bunyavirales order; infectious disease; biochemistry; inter-spike interface; microbiology; viral breathing; virus; envelope proteins; membrane fusion
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.46028

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.