A Funneled Conformational Landscape Governs Flavivirus Fusion Peptide Interaction with Lipid Membranes.

摘要: During host cell infection by flaviviruses such as dengue and Zika, acidic pH within the endosome triggers a conformational change in envelope protein on outer surface of virion. This results exposure ∼15 residue fusion peptide (FP) region, freeing it to induce between viral endosomal membranes. A better understanding dynamics FP presence membranes, basis for its selectivity anionic lipid species present endosome, would facilitate therapeutic targeting with antiviral drugs antibodies. In this work, multiscale modeling, simulations, free energy calculations (including total ∼75 μs atomic-resolution sampling), combined imaging internal reflection fluorescence correlation spectroscopy experiments, were employed investigate mechanisms interaction variants bilayers. Wild-type FPs (in or absence fluorescein isothiocyanate tag) shown t...