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| Verfasst von: | Parisotto, Daniel [VerfasserIn]  |
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| | Pfau, Maximilian [VerfasserIn] |
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| | Malsam, Andrea [VerfasserIn] |
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| | Wild, Klemens [VerfasserIn] |
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| | Mayer, Matthias P. [VerfasserIn] |
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| | Malsam, Jörg [VerfasserIn] |
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| | Sinning, Irmgard [VerfasserIn] |
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| | Söllner, Thomas [VerfasserIn] |
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| Titel: | An extended helical conformation in domain 3a of Munc18-1 provides a template for SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) complex assembly |
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| Verf.angabe: | Daniel Parisotto, Maximilian Pfau, Andrea Scheutzow, Klemens Wild, Matthias P. Mayer, Jörg Malsam, Irmgard Sinning, and Thomas H. Söllner |
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| E-Jahr: | 2014 |
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| Jahr: | February 14, 2014 |
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| Umfang: | 12 S. |
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| Fussnoten: | Gesehen am 04.09.2020 |
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| Titel Quelle: | Enthalten in: The journal of biological chemistry |
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| Ort Quelle: | Bethesda, Md. : ASBMB Publications, 1905 |
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| Jahr Quelle: | 2014 |
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| Band/Heft Quelle: | 289(2014), 14, Seite 9639-9650 |
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| ISSN Quelle: | 1083-351X |
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| Abstract: | Munc18-1, a SEC1/Munc18 protein and key regulatory protein in synaptic transmission, can either promote or inhibit SNARE complex assembly. Although the binary inhibitory interaction between Munc18-1 and closed syntaxin 1 is well described, the mechanism of how Munc18-1 stimulates membrane fusion remains elusive. Using a reconstituted assay that resolves vesicle docking, priming, clamping, and fusion during synaptic exocytosis, we show that helix 12 in domain 3a of Munc18-1 stimulates SNAREpin assembly and membrane fusion. A single point mutation (L348R) within helix 12 selectively abolishes VAMP2 binding and the stimulatory function of Munc18-1 in membrane fusion. In contrast, targeting a natural switch site (P335A) at the start of helix 12, which can result in an extended α-helical conformation, further accelerates lipid-mixing. Together with structural modeling, the data suggest that helix 12 provides a folding template for VAMP2, accelerating SNAREpin assembly and membrane fusion. Analogous SEC1/Munc18-SNARE interactions at other transport steps may provide a general mechanism to drive lipid bilayer merger. At the neuronal synapse, Munc18-1 may convert docked synaptic vesicles into a readily releasable pool. |
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| DOI: | doi:10.1074/jbc.M113.514273 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1074/jbc.M113.514273 |
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| | Volltext: http://www.jbc.org/content/289/14/9639 |
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| | DOI: https://doi.org/10.1074/jbc.M113.514273 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Exocytosis |
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| | Membrane Fusion |
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| | Membrane Reconstitution |
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| | Membrane Trafficking |
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| | SM Protein |
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| | Snare Proteins |
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| | Synaptic Vesicle |
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| | VAMP2/Synaptobrevin |
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| K10plus-PPN: | 1728890918 |
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| Verknüpfungen: | → Zeitschrift |
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¬An¬ extended helical conformation in domain 3a of Munc18-1 provides a template for SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor) complex assembly / Parisotto, Daniel [VerfasserIn]; February 14, 2014 (Online-Ressource)
