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Hofmann, MW, Peplowska, K, Rohde, J, Poschner, BC, Ungermann, C and Langosch, D (2006) Self-interaction of a SNARE transmembrane domain promotes the hemifusion-to-fusion transition. J. Mol. Biol. 364:1048-60


SNARE proteins mediate intracellular fusion of eukaryotic membranes. Some SNAREs have previously been shown to dimerise via interaction of their transmembrane domains. However, the functional significance of these interactions had remained unclear. Here, we show that mutating alternate faces of the transmembrane helix of the yeast vacuolar Q-SNARE Vam3p reduces the ability of the full-length protein to induce contents mixing in yeast vacuole fusion to different extents. Examination of liposome fusion induced by synthetic transmembrane domains revealed that inner leaflet mixing is delayed relative to outer leaflet mixing, suggesting that fusion transits through a hemifusion intermediate. Interestingly, one of the mutations impaired inner leaflet mixing in the liposome system. This suggests that the defect seen in vacuolar contents mixing is due to partial arrest of the reaction at hemifusion. Since covalent dimerisation of this mutant recovered wild-type behaviour, homodimerisation of a SNARE transmembrane domain appears to control the transition of a hemifusion intermediate to complete lipid mixing.


PubMed Online version:10.1016/j.jmb.2006.09.077


Circular Dichroism; Cross-Linking Reagents; Intracellular Membranes/metabolism; Lipid Bilayers/chemistry; Lipid Bilayers/metabolism; Liposomes/chemistry; Liposomes/metabolism; Membrane Fusion; Mutagenesis, Site-Directed; Mutation/genetics; Peptide Fragments/chemistry; Peptide Fragments/metabolism; Qa-SNARE Proteins/chemistry; Qa-SNARE Proteins/genetics; Qa-SNARE Proteins/metabolism; Saccharomyces cerevisiae/cytology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Spectrometry, Mass, Electrospray Ionization; Vacuoles/chemistry; Vacuoles/metabolism



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status



GO:0005484: SNAP receptor activity

ECO:0000314: direct assay evidence used in manual assertion


Seeded From UniProt


See also


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