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The Energetics of Membrane Fusion from Binding, through Hemifusion, Pore Formation, and Pore Enlargement

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Abstract

The main steps of viral membrane fusion are local membrane approach, hemifusion, pore formation, and pore enlargement. Experiments and theoretical analyses have helped determine the relative energies required for each step. Key protein structures and conformational changes of the fusion process have been identified. The physical deformations of monolayer bending and lipid tilt have been applied to the steps of membrane fusion. Experiment and theory converge to strongly indicate that, contrary to former conceptions, the fusion process is progressively more energetically difficult: hemifusion has a relatively low energy barrier, pore formation is more energy-consuming, and pore enlargement is the most difficult to achieve.

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Acknowledgments

We thank Drs. Leonid Chernomordik, Yuri Chizmadzhev, Michael Kozlov, Peter Kuzmin, and Joshua Zimmerberg for discussions over many years on the theory of membrane mechanics and its application to membrane fusion. This work was supported by National Institutes of Health grants GM-27367 and GM-54787.

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  1. Department of Molecular Biophysics and Physiology, Rush University Medical Center, 1653 W Congress Parkway, Chicago, IL, 60612, USA

    F.S. Cohen & G.B. Melikyan

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Correspondence to F.S. Cohen.

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Cohen, F., Melikyan, G. The Energetics of Membrane Fusion from Binding, through Hemifusion, Pore Formation, and Pore Enlargement. J Membrane Biol 199, 1–14 (2004). https://doi.org/10.1007/s00232-004-0669-8

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