Oligomeric states of an Influenza-encoded PB1-F2 viroporin

Abstract

Influenza Viruses have always been a major health concern due to their highly contagious nature. The PB1-F2 viroporin encoded by the influenza A virus is known to be a pro-apoptotic protein involved in cell death induction of the host immune cells. The structural arrangement and the mode of action of PB1-F2 viroporin have not been fully understood. In this study, we report on the most probable oligomeric structural existences of PB1-F2, investigated by Molecular Dynamics Simulations with improved sampling of conformational states. The simulations provide a channel framework to study the mitochondrial membrane permeation pathway which could initiate the leakage of mitochondrial contents like cytochrome C and induce apoptosis. The structural attributes of the oligomeric states were rigorously evaluated by comparing the experimental reports. Our results reveal a tetrameric form as the preferable state in the lipid environment. This further fulfills the ion transportation criteria by providing a less energetic barrier to ions/water molecules crossing the membrane.