The SNAP-25 linker supports fusion intermediates by local lipid interactions
| Autor: | Ute Becherer, Ali H Shaib, Ali Harb, Ahmed Shaaban, Madhurima Dhara, Walentina Frisch, Dieter Bruns, Ralf Mohrmann |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Synaptosomal-Associated Protein 25 Mouse QH301-705.5 Science Chromaffin Cells DNA Mutational Analysis Phospholipid fusion triggering General Biochemistry Genetics and Molecular Biology Exocytosis SNARE complex 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Animals Secretion fusion pore Biology (General) Ternary complex Cells Cultured Phospholipids General Immunology and Microbiology General Neuroscience Fusion Complex Vesicle Secretory Vesicles General Medicine Cell Biology Rats 030104 developmental biology chemistry Biophysics SNAP-25 Medicine Female Protein Multimerization SNARE Proteins exocytosis Linker 030217 neurology & neurosurgery Protein Binding Research Article Neuroscience |
| Zdroj: | eLife eLife, Vol 8 (2019) |
| ISSN: | 2050-084X |
| Popis: | SNAP-25 is an essential component of SNARE complexes driving fast Ca2+-dependent exocytosis. Yet, the functional implications of the tandem-like structure of SNAP-25 are unclear. Here, we have investigated the mechanistic role of the acylated “linker” domain that concatenates the two SNARE motifs within SNAP-25. Refuting older concepts of an inert connector, our detailed structure-function analysis in murine chromaffin cells demonstrates that linker motifs play a crucial role in vesicle priming, triggering, and fusion pore expansion. Mechanistically, we identify two synergistic functions of the SNAP-25 linker: First, linker motifs support t-SNARE interactions and accelerate ternary complex assembly. Second, the acylated N-terminal linker segment engages in local lipid interactions that facilitate fusion triggering and pore evolution, putatively establishing a favorable membrane configuration by shielding phospholipid headgroups and affecting curvature. Hence, the linker is a functional part of the fusion complex that promotes secretion by SNARE interactions as well as concerted lipid interplay. |
| Databáze: | OpenAIRE |
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