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Energetics and dynamics of SNAREpin folding across lipid bilayers

Nature Structural & Molecular Biology volume 14, pages 890–896 (2007)Cite this article

Abstract

Membrane fusion occurs when SNAREpins fold up between lipid bilayers. How much energy is generated during SNAREpin folding and how this energy is coupled to the fusion of apposing membranes is unknown. We have used a surface forces apparatus to determine the energetics and dynamics of SNAREpin formation and characterize the different intermediate structures sampled by cognate SNAREs in the course of their assembly. The interaction energy–versus–distance profiles of assembling SNAREpins reveal that SNARE motifs begin to interact when the membranes are 8 nm apart. Even after very close approach of the bilayers (∼2–4 nm), the SNAREpins remain partly unstructured in their membrane-proximal region. The energy stabilizing a single SNAREpin in this configuration (35 kBT) corresponds closely with the energy needed to fuse outer but not inner leaflets (hemifusion) of pure lipid bilayers (40–50 kBT).

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Figure 1: Interaction energy–versus–distance profile of cognate SNAREs in apposing bilayers (squares, approach; circles, separation).
Figure 2: Specificity and kinetics of SNARE assembly.
Figure 3: Energy of SNAREpin folding.
Figure 4: Extent of SNAREpin folding.
Figure 5: SNARE assembly and adhesion energy are modulated by SNARE-membrane interactions.

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Acknowledgements

This work was supported by the Human Frontier Science Program, a travel grant from US National Science Foundation, and US National Institutes of Health grants to J.E.R. We thank J. McNew (Rice University) for the generous gift of the plasmids used in this study, and A. Martin-Molina, A. Yamamoto and D. You for experimental help and many fruitful discussions.

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Authors and Affiliations

  1. Laboratoire de Physique Statistique, Unité Mixte de Recherche 8550, Centre National de la Recherche Scientifique associée aux Universités Paris VI et Paris VII, Ecole Normale Supérieure, 24 rue Lhomond, Paris, 75005, France

    Feng Li, Frédéric Pincet & Eric Perez

  2. Department of Physiology and Cellular Biophysics, Columbia University, 1150 Saint Nicholas Avenue, New York, 10032, New York, USA

    William S Eng, Thomas J Melia, James E Rothman & David Tareste

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  1. Feng Li
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Correspondence to David Tareste.

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Li, F., Pincet, F., Perez, E. et al. Energetics and dynamics of SNAREpin folding across lipid bilayers. Nat Struct Mol Biol 14, 890–896 (2007). https://doi.org/10.1038/nsmb1310

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