Regulation of Ebola GP conformation and membrane binding by the chemical environment of the late endosome

• DOI: 10.1371/journal.ppat.1011848
• Publication Date: 2023-12-06T18:44:13Z
• Authors: Aastha Jain; Ramesh Govindan; Alex R. Berkman; Jeremy Luban; Marco A. Díaz-Sal...; Natasha D. Durham; James B. Munro
• Keywords: Chemical Biology

Interaction between the Ebola virus envelope glycoprotein (GP) and endosomal membrane is an essential step during entry into cell. Acidic pH Ca2+ have been implicated in mediating GP-membrane interaction. However, molecular mechanism by which these environmental factors regulate conformational changes that enable engagement of GP with target unknown. Here, we apply fluorescence correlation spectroscopy (FCS) single-molecule Förster resonance energy transfer (smFRET) imaging to elucidate how acidic pH, anionic phospholipids late endosome promote interaction, thereby facilitating entry. We find bis(monoacylglycero)phosphate (BMP), specific endosome, especially critical determining Ca2+-dependence Molecular dynamics (MD) simulations suggested residues sense induce make fusion loop available for insertion membrane. similarly confirm mediate GP's interaction Ca2+, likely promotes local mediates electrostatic interactions phospholipids. Collectively, our results provide a mechanistic understanding environment regulates timing efficiency