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Structure and function of the complete internal fusion loop from Ebolavirus glycoprotein 2
Sonia M Gregory1, Erisa Harada, Binyong Liang
1Center for Membrane Biology, University of Virginia, Charlottesville, VA 22908, USA.
Ebolavirus glycoprotein
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Ebolavirus (Ebov) causes hemorrhagic fever.
- Viral glycoprotein (GP) mediates virus-host membrane fusion.
- GP priming by cathepsins in endosomes is essential for fusion.
Purpose of the Study:
- To elucidate the mechanism of Ebolavirus internal fusion loop (FL) in membrane fusion.
- To determine the structural basis of FL-mediated fusion.
Main Methods:
- Liposome fusion assays.
- Nuclear Magnetic Resonance (NMR) spectroscopy.
- Circular dichroism (CD) experiments.
Main Results:
- The Ebov FL induced rapid liposome fusion at pH ≤5.5.
- Low pH induced an α-helical conformational change in the FL.
- NMR revealed a pH-dependent structural bend in the FL, reorienting its hydrophobic patch.
Conclusions:
- The Ebov FL undergoes a low-pH-induced conformational change critical for fusion.
- This structural transition facilitates membrane disruption and initiates Ebolavirus fusion.
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