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Structural transitions of the conserved and metastable hantaviral glycoprotein envelope

DOI: 10.1128/JVI.00378-17 DOI Help

Authors: Ilona Rissanen (Wellcome Trust Centre for Human Genetics, University of Oxford) , Robert Stass (Wellcome Trust Centre for Human Genetics, University of Oxford) , Antra Zeltina (Wellcome Trust Centre for Human Genetics, University of Oxford) , Sai Li (Wellcome Trust Centre for Human Genetics, University of Oxford) , Jussi Hepojoki (University of Z├╝rich; University of Helsinki) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , Robert J. C. Gilbert (Wellcome Trust Centre for Human Genetics, University of Oxford) , Juha Huiskonen (Wellcome Trust Centre for Human Genetics, University of Oxford; University of Helsinki) , Thomas A. Bowden (Wellcome Trust Centre for Human Genetics, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Virology

State: Published (Approved)
Published: August 2017
Diamond Proposal Number(s): 10627

Open Access Open Access

Abstract: Hantaviruses are zoonotic pathogens with a near-global distribution that can cause severe hemorrhagic fever and pulmonary syndrome. The outer membrane of the hantavirus envelope displays a lattice of two glycoproteins, Gn and Gc, which orchestrate host cell recognition and entry. Here, we describe the crystal structure of the Gn glycoprotein ectodomain from the Asiatic Hantaan virus (HTNV), the most prevalent pathogenic hantavirus. Structural overlay analysis reveals that the HTNV Gn fold is highly similar to the Gn of Puumala virus (PUUV), a genetically and geographically distinct and less pathogenic hantavirus found predominantly in North-Eastern Europe, confirming that the hantaviral Gn fold is architecturally conserved across hantavirus clades. Interestingly, HTNV Gn crystallized at acidic pH, in a compact tetrameric configuration distinct from the organization at neutral pH. Analysis of the Gn, both in solution and in the context of the virion, confirms the pH-sensitive oligomeric nature of the glycoprotein, indicating that the hantaviral Gn undergoes structural transitions during host cell entry. These data allow us to present a structural model for how acidification during endocytic uptake of the virus triggers the dissociation of the metastable Gn-Gc lattice to enable insertion of the Gc-resident hydrophobic fusion loops into the host cell membrane. Together, these data reveal the dynamic plasticity of the structurally conserved hantaviral surface.

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I04-Macromolecular Crystallography

Added On: 29/08/2017 11:25

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JVI.00378-17.full.pdf

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