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Int. J. Mol. Sci. 2017, 18(12), 2598; doi:10.3390/ijms18122598

Switching between Successful and Dead-End Intermediates in Membrane Fusion

Laboratory of Bioelectrochemistry, A.N. Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 31/4 Leninskiy Prospekt, 119071 Moscow, Russia
Department of Theoretical Physics and Quantum Technologies, National University of Science and Technology “MISiS”, 4 Leninskiy Prospekt, 119049 Moscow, Russia
Department of Engineering of Technological Equipment, National University of Science and Technology “MISiS”, 4 Leninskiy Prospekt, 119049 Moscow, Russia
Laboratory of Electrophysiology, Federal Clinical Center of Physical-Chemical Medicine of FMBA, 1a Malaya Pirogovskaya Street, 119435 Moscow, Russia
Department of Physics of Living Systems, Moscow Institute of Physics and Technology (State University), 9 Institutskiy Lane, 141700 Dolgoprudniy Moscow Region, Russia
These authors contributed equally to the work.
Author to whom correspondence should be addressed.
Received: 31 October 2017 / Revised: 21 November 2017 / Accepted: 1 December 2017 / Published: 2 December 2017
(This article belongs to the Special Issue Membrane Fusion)
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Fusion of cellular membranes during normal biological processes, including proliferation, or synaptic transmission, is mediated and controlled by sophisticated protein machinery ensuring the preservation of the vital barrier function of the membrane throughout the process. Fusion of virus particles with host cell membranes is more sparingly arranged and often mediated by a single fusion protein, and the virus can afford to be less 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 formation of π-shaped structures was suggested. In this study, we apply the methods of elasticity theory and Lagrangian formalism augmented by phenomenological and molecular geometry constraints and boundary conditions to investigate the traits of this trajectory and the drivers behind the choice of one of the possible scenarios depending on the properties of the system. The alternative pathway proved to be a dead end, and, depending on the parameters of the participating membranes and fusion proteins, the system can either reversibly enter the corresponding “leaky” configuration or be trapped in it. A parametric study in the biologically relevant range of variables emphasized the fusion protein properties crucial for the choice of the fusion scenario. View Full-Text
Keywords: membrane fusion; viral fusion; enveloped viruses; fusion peptides; stalk mechanism; dead-end state membrane fusion; viral fusion; enveloped viruses; fusion peptides; stalk mechanism; dead-end state

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Molotkovsky, R.J.; Galimzyanov, T.R.; Jiménez-Munguía, I.; Pavlov, K.V.; Batishchev, O.V.; Akimov, S.A. Switching between Successful and Dead-End Intermediates in Membrane Fusion. Int. J. Mol. Sci. 2017, 18, 2598.

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