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Lipid composition of the membrane and the depth of embedding of the fusion peptide are regulators of membrane fusion

Molotkovsky R.J., Galimzyanov T.R.1, Batischev O.V.

Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Moscow, 119071

1National University of Science and Technology "MISiS", Moscow, 119049, Russia

The fusion of virus particles with host cell membranes during the viral infection process is mediated and controlled by sophisticated protein machinery. It is believed this machinery preserves the vital barrier function of the membrane throughout the process. However, the virus can afford to be not so discriminative towards the possible different outcomes of fusion attempts. Formation of leaky intermediates was recently observed in some fusion processes, and an alternative trajectory of the process involving the formation of π-shaped structures was suggested. In this study we analyze two possible trajectories of the fusion process: the first one corresponds to the non-leaky fusion and formation of the stalk, and the other to the formation of a pore and -shaped structure. We show that an increase in the protein force, peptide-induced membrane perturbation and cholesterol concentration promotes the stalk formation by lowering required energy barrier. The results obtained indicate that these three characteristics have a deep interconnection. In the case when force is not enough to lower the energy barrier for the stalk formation, it is compensated by a more favourable structure for the peptide inclusion into the membrane and by the requirement of a specific composition of this membrane.

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