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  Expansion of the fusion stalk and its implication for biological membrane fusion.

Risselada, H. J., Bubnis, G., & Grubmüller, H. (2014). Expansion of the fusion stalk and its implication for biological membrane fusion. Proceedings of the National Academy of Sciences of the United States of America, 111(30), 11043-11048. doi:10.1073/pnas.1323221111.

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Risselada, H. J.1, Author           
Bubnis, G.1, Author           
Grubmüller, H.1, Author           
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1Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society, ou_578631              

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Free keywords: SNARE; diaphragm; hemagglutinin; hemi; neuronal
 Abstract: Over the past 20 years, it has been widely accepted that membrane fusion proceeds via a hemifusion step before opening of the productive fusion pore. An initial hourglass-shaped lipid structure, the fusion stalk, is formed between the adjacent membrane leaflets (cis leaflets). It remains controversial if and how fusion proteins drive the subsequent transition (expansion) of the stalk into a fusion pore. Here, we propose a comprehensive and consistent thermodynamic understanding in terms of the underlying free-energy landscape of stalk expansion. We illustrate how the underlying free energy landscape of stalk expansion and the concomitant pathway is altered by subtle differences in membrane environment, such as leaflet composition, asymmetry, and flexibility. Nonleaky stalk expansion (stalk widening) requires the formation of a critical trans-leaflet contact. The fusion machinery can mechanically enforce trans-leaflet contact formation either by directly enforcing the trans-leaflets in close proximity, or by (electrostatically) condensing the area of the cis leaflets. The rate of these fast fusion reactions may not be primarily limited by the energetics but by the forces that the fusion proteins are able to exert.

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Language(s): eng - English
 Dates: 2014-07-142014-07-29
 Publication Status: Issued
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.1323221111
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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Pages: - Volume / Issue: 111 (30) Sequence Number: - Start / End Page: 11043 - 11048 Identifier: -