Structural changes of envelope proteins during alphavirus fusion
Long Li1, Joyce Jose, Ye Xiang
1Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, Indiana 47907-2054, USA.
Nature
|December 3, 2010
Summary
This study reveals the low-pH structure of alphavirus spikes, showing an intermediate state during viral fusion. This clarifies how E1 glycoprotein mediates membrane fusion after E2 protein dissociates.
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Alphaviruses are lethal RNA viruses that enter host cells via endocytosis.
- Viral entry is mediated by E1 and E2 envelope glycoproteins forming trimeric spikes.
- E1 facilitates membrane fusion, while E2 binds receptors and shields E1 at neutral pH.
Purpose of the Study:
- To determine the low-pH structure of an alphavirus spike.
- To elucidate the intermediate conformational changes during viral fusion.
- To clarify the alphavirus maturation process.
Main Methods:
- Crystallization of alphavirus spike protein at low pH.
- X-ray crystallography to determine the 3D structure.
- Analysis of structural changes related to viral fusion.
Main Results:
- The low-pH structure represents an intermediate in the fusion process.
- E2 and E1 glycoproteins dissociate, exposing the E1 fusion loop.
- E1 forms homotrimers, initiating viral and endosomal membrane fusion.
- E2 protein exhibits immunoglobulin-like folds, consistent with receptor binding.
Conclusions:
- The determined structure clarifies the alphavirus maturation and fusion mechanism.
- Understanding this process is crucial for developing antiviral strategies.
- Structural insights into E1-E2 interactions inform future drug design.
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