Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins Journal Article
| Authors: | Melia, T. J.; Weber, T.; Mcnew, J. A.; Fisher, L. E.; Johnston, R. J.; Parlati, F.; Mahal, L.; Söllner, T. H.; Rothman, J. E. |
| Article Title: | Regulation of membrane fusion by the membrane-proximal coil of the t-SNARE during zippering of SNAREpins |
| Abstract: | We utilize structurally targeted peptides to identify a "tc fusion switch" inherent to the coil domains of the neuronal t-SNARE that pairs with the cognate v-SNARE. The tc fusion switch is located in the membrane-proximal portion of the t-SNARE and controls the rate at which the helical bundle that forms the SNARE-pin can zip up to drive bilayer fusion. When the fusion switch is "off" (the intrinsic state of the t-SNARE), zippering of the helices from their membrane-distal ends is impeded and fusion is slow. When the tc fusion switch is "on," fusion is much faster. The tc fusion switch can be thrown by a peptide that corresponds to the membrane-proximal half of the cognate v-SNARE, and binds reversibly to the cognate region of the t-SNARE. This structures the coil in the membrane-proximal domain of the t-SNARE and accelerates fusion, implying that the intrinsically unstable coil in that region is a natural impediment to the completion of zippering, and thus, fusion. Proteins that stabilize or destabilize one or the other state of the tc fusion switch would exert fine temporal control over the rate of fusion after SNAREs have already partly zippered up. |
| Keywords: | protein expression; protein conformation; animals; mice; models, biological; carboxy terminal sequence; protein assembly; protein degradation; nerve tissue proteins; protein binding; membrane proteins; time factors; blotting, western; amino acid sequence; molecular sequence data; protein purification; western blotting; cell membrane; binding site; binding sites; rats; protein folding; liposome; liposomes; lipid bilayer; electrophoresis; antigens, surface; vesicular transport proteins; membrane lipids; membrane fusion; synaptosome; vesicle; snare protein; syntaxin; syntaxin 1; r-snare proteins; snare proteins; synaptosomal-associated protein 25; synaptosomal associated protein 25; priority journal; article; snap-25; vamp; proteinase k |
| Journal Title: | Journal of Cell Biology |
| Volume: | 158 |
| Issue: | 5 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2002-09-03 |
| Start Page: | 929 |
| End Page: | 940 |
| Language: | English |
| DOI: | 10.1083/jcb.200112081 |
| PUBMED: | 12213837 |
| PROVIDER: | scopus |
| PMCID: | PMC2173141 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
