Conformational changes of the flavivirus E glycoprotein

Area of Science:

• Structural virology
• Molecular biology
• Biophysics

Background:

• Dengue virus, a Flaviviridae family member, possesses a surface with 180 copies each of envelope (E) glycoprotein and membrane (M) protein.
• Understanding the E glycoprotein's structure and dynamics is key to comprehending flavivirus assembly and infection mechanisms.

Purpose of the Study:

• To determine the crystal structure of an N-terminal fragment of the Dengue virus E glycoprotein.
• To compare this structure with previously described conformations and analyze its fitting into cryo-electron microscopy maps of dengue virus particles.

Main Methods:

• X-ray crystallography was used to determine the structure of an E glycoprotein fragment.
• Rigid body fitting of E structures into cryo-electron microscopy maps of immature and mature dengue virus particles.
• Comparison of E glycoprotein structures in different states (crystal, immature virion, mature virion).

Main Results:

• A 10-degree rotation was identified between two rigid body components of the E glycoprotein structure.
• Fitting E structures into cryo-EM maps revealed a 27-degree difference between components in immature and mature dengue viruses.
• Comparison with the postfusion state indicated rotation around the same hinge, suggesting conformational flexibility.

Conclusions:

• The Dengue virus E glycoprotein exhibits significant conformational flexibility.
• This flexibility, involving rotation around a specific hinge, is essential for both virus assembly and host cell infection.
• Structural dynamics of the E glycoprotein are a critical functional requirement for flaviviruses.