Title: Structural determinants of influenza virus fusion peptide activity

Date: 26th February 2021 (Friday)

Time: 12:00 pm (Central European Time)

Host: prof. Joanna Trylska

Virtual seminar: https://us02web.zoom.us/j/85624784389

Meeting ID: 856 2478 4389

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Abstract:

Membrane fusion is necessary for the entrance of influenza virus into host cell. It is mediated by the hemagglutinin protein, whose N-terminal fragments of only 20-23 amino acids length have long been known to induce fusion on their own and are thus called fusion peptides. Accumulated data suggest that influenza fusion peptides adopt kinked structures whose actual bending angle and orientation within the membrane vary depending on a number of subtle factors. One of them are amino acids mutations, in particular those that lead to fusion deficient phenotype. In spite of ongoing efforts, the details of peptide-lipid interactions and their role in membrane fusion remain elusive, hampering our understanding of this key event in viral life cycle.

Using the combination of extensive all atom, explicit solvent molecular dynamics simulations and experimental methods we investigate peptides free energy landscape, lipid order perturbation, and fusion efficacy. We suggest that peptides activity may be directly related to their ability to at least transiently penetrate membrane core, and we demonstrate that this ability is lost as an effect of a known, function-loss W14A mutation. Our findings provide physical interpretation for structure-activity relationships for variants of influenza fusion peptide, thus contributing to understanding of fusion mechanism.