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Updated: May 9, 2026
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Sample Preparation for Single Virion Atomic Force Microscopy and Super-resolution Fluorescence Imaging
Published on: January 2, 2014
Control of viral envelope glycoprotein function revealed by single-molecule imaging
Matthew Unger1, James B Munro1
1Department of Microbiology, UMass Chan Medical School, Worcester, MA 01605, USA; Department of Biochemistry and Molecular Biotechnology, UMass Chan Medical School, Worcester, MA 01605, USA.
Current Opinion in Structural Biology
|May 7, 2026
Summary
Viral envelope glycoproteins dynamically adjust their pre-fusion shapes, influenced by the host environment. This thermodynamic control, revealed by single-molecule Förster resonance energy transfer (smFRET), precedes the fusion process, impacting viral entry.
Area of Science:
- Biophysics
- Virology
- Molecular Biology
Background:
- Viral envelope glycoproteins mediate cell entry through membrane fusion.
- Traditionally, this process was understood via kinetic control, involving irreversible conformational changes triggered by environmental cues like pH.
- Emerging evidence suggests a more complex regulatory mechanism involving pre-fusion dynamics.
Purpose of the Study:
- To investigate the role of thermodynamic control in the conformational dynamics of viral envelope glycoproteins.
- To explore how environmental factors modulate the pre-fusion energy landscape of these glycoproteins.
- To understand the implications of these dynamics for viral entry and fitness.
Main Methods:
- Utilized single-molecule Förster resonance energy transfer (smFRET) imaging.
- Applied smFRET to study envelope glycoproteins from multiple viruses, including HIV-1, SARS-CoV-2, MERS-CoV, Ebola virus, and influenza A virus.
- Analyzed the conformational ensembles and their response to various stimuli.
Main Results:
- Demonstrated that viral envelope glycoproteins dynamically sample an ensemble of pre-fusion conformations.
- Showed that the relative stabilities of these conformations are sensitive to pH, receptor binding, ions, and host proteases.
- Revealed that this thermodynamic tuning precedes the kinetically controlled fusion event.
Conclusions:
- Single-molecule FRET imaging has unveiled a crucial layer of thermodynamic control governing viral glycoprotein pre-fusion dynamics.
- The pre-fusion energy landscape is actively tuned by the host environment, influencing viral entry efficiency.
- This nuanced understanding of glycoprotein conformational dynamics is vital for comprehending viral fitness and developing antiviral strategies.
