Transition between successful and deadlock intermediates at the initial stage of membrane fusion

Molotkovsky R.J., Galimzyanov T.R.1, Akimov S.A.1

A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 31/4 Leninskiy pr. 119071 Moscow, Russia

1National University of Science and Technology “MISiS”, 4 Leninskiy pr. 119049 Moscow, Russia

The fusion of cell membranes during biological processes is mediated and controlled by a complex protein mechanism that ensures the preservation of membrane barrier function throughout the process. The fusion of virus particles with the membrane of the target cell is more economically organized and often mediated by a single fusion protein. Recently, the formation of leakage intermediate structures in some fusion processes was discovered, and an alternative trajectory of the process was proposed with the formation of pi-shaped structures. We apply the methods of the theory of elasticity and the Lagrangian formalism, supplemented by phenomenological and molecular geometric constraints and boundary conditions. We investigate the influence of the structure of these proteins on the choice of the trajectory of the process of membrane interaction. We show that the alternative structure turns out to be a dead-end intermediate, and depending on the parameters of the participating membranes and fusion proteins, it can be either reversible or irreversible. We show that the structure of the fusion peptides that are inserted in the membrane of the target cell exerts the greatest influence on the fusion process. The behavior of the system is mostly determined by the depth of insertion of the peptide. Our results explain a number of experimental data showing the correlation between the depth of insertion of the fusion peptide and the fusion efficiency mediated by this peptide: the deeper is the insertion, the more efficient is the fusion of membranes.

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