t-SNARE protein conformations patterned by the lipid microenvironment

Rickman, Colin and Medine, Claire N and Dun, Alison R and Moulton, David J and Mandula, Ondrej and Halemani, Nagaraj D and Rizzoli, Silvio O and Chamberlain, Luke H and Duncan, Rory R (2010) t-SNARE protein conformations patterned by the lipid microenvironment. Journal of Biological Chemistry, 285 (18). pp. 13535-13541. ISSN 1083-351X (https://doi.org/10.1074/jbc.M109.091058)

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Abstract

The spatial distribution of the target (t-)SNARE proteins (syntaxin and SNAP-25) on the plasma membrane has been extensively characterized. However, the protein conformations and interactions of the two t-SNAREs in situ remain poorly defined. By using super-resolution optical techniques and fluorescence lifetime imaging microscopy, we observed that within the t-SNARE clusters syntaxin and SNAP-25 molecules interact, forming two distinct conformations of the t-SNARE binary intermediate. These are spatially segregated on the plasma membrane with each cluster exhibiting predominantly one of the two conformations, representing the two- and three-helical forms previously observed in vitro. We sought to explain why these two t-SNARE intermediate conformations exist in spatially distinct clusters on the plasma membrane. By disrupting plasma membrane lipid order, we found that all of the t-SNARE clusters now adopted a single conformational state corresponding to the three helical t-SNARE intermediates. Together, our results define spatially distinct t-SNARE intermediate states on the plasma membrane and how the conformation adopted can be patterned by the underlying lipid environment.

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