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 1083-351XFull text not available in this repository. (Request a copy from the Strathclyde author)
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.
|Keywords:||animals, cell membrane, membrane lipids, PC12 cells, protein structure, quaternary, protein structure, secondary, Qa-SNARE proteins, rats, synaptosomal-associated protein 25, Therapeutics. Pharmacology, Biochemistry, Cell Biology, Molecular Biology|
|Subjects:||Medicine > Therapeutics. Pharmacology|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Pure Administrator|
|Date Deposited:||10 Aug 2011 09:28|
|Last modified:||17 Feb 2017 05:17|