Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses

Area of Science:

• Virology
• Structural Biology
• Biochemistry

Background:

• Sindbis virus is an enveloped virus with a non-segmented positive-sense single-stranded RNA genome.
• Its surface glycoproteins, E1 and E2, are crucial for host cell entry and interaction.
• Understanding the structural basis of viral fusion is key to developing antiviral strategies.

Purpose of the Study:

• To determine the high-resolution structure of the Sindbis virus.
• To elucidate the structural organization and interactions of viral glycoproteins E1 and E2.
• To characterize conformational changes during virus-host cell fusion.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to generate a 9 Å resolution map.
• Analysis of the map provided information on polypeptide topology and protein-protein interactions.
• Marker positions on the E2 protein were utilized to establish its topology.

Main Results:

• Detailed structural information on the E2 protein's polypeptide topology was obtained.
• Interactions between E1 and E2 glycoproteins forming a heterodimer were characterized.
• Conformational differences in trimeric spikes and E1-E2 transmembrane helix interactions were identified.
• Significant conformational changes, including E2 monomer rotation, during fusion were observed.

Conclusions:

• The study provides a high-resolution structural model of Sindbis virus glycoproteins.
• These findings offer insights into the molecular mechanisms of viral fusion and entry.
• The conformational plasticity of spikes and E2 monomers is critical for host cell interaction and fusion.