5OPG

Structure of the Hantaan virus Gn glycoprotein ectodomain

5OPG の概要

• エントリーDOI: 10.2210/pdb5opg/pdb
• 分子名称: envelope glycoprotein Gn, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: glycoprotein, gn, hantavirus envelope, bunyavirus, viral entry, viral attachment, viral protein
• 由来する生物種: Hantaan orthohantavirus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41842.70

構造登録者

Rissanen, I.,Stass, R.,Zeltina, A.,Li, S.,Hepojoki, J.,Harlos, K.,Gilbert, R.J.C.,Huiskonen, J.T.,Bowden, T.A. (登録日: 2017-08-09, 公開日: 2017-08-23, 最終更新日: 2024-11-20)

主引用文献

Rissanen, I.,Stass, R.,Zeltina, A.,Li, S.,Hepojoki, J.,Harlos, K.,Gilbert, R.J.C.,Huiskonen, J.T.,Bowden, T.A.
Structural Transitions of the Conserved and Metastable Hantaviral Glycoprotein Envelope.
J. Virol., 91:-, 2017

PubMed Abstract: Hantaviruses are zoonotic pathogens that 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 northeastern 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. Although outbreaks of Korean hemorrhagic fever were first recognized during the Korean War (1950 to 1953), it was not until 1978 that they were found to be caused by Hantaan virus (HTNV), the most prevalent pathogenic hantavirus. Here, we describe the crystal structure of HTNV envelope glycoprotein Gn, an integral component of the Gn-Gc glycoprotein spike complex responsible for host cell entry. HTNV Gn is structurally conserved with the Gn of a genetically and geographically distal hantavirus, Puumala virus, indicating that the observed α/β fold is well preserved across the family. The combination of our crystal structure with solution state analysis of recombinant protein and electron cryo-microscopy of acidified hantavirus allows us to propose a model for endosome-induced reorganization of the hantaviral glycoprotein lattice. This provides a molecular-level rationale for the exposure of the hydrophobic fusion loops on the Gc, a process required for fusion of viral and cellular membranes.

PubMed: 28835498
DOI: 10.1128/JVI.00378-17

実験手法

X-RAY DIFFRACTION (2.15 Å)