Online-Ressource | |
Verfasst von: | André, Timon [VerfasserIn] |
Classen, Jessica [VerfasserIn] | |
Brenner, Philipp [VerfasserIn] | |
Betts, Matthew J. [VerfasserIn] | |
Dörr, Bernhard [VerfasserIn] | |
Kreye, Susanne [VerfasserIn] | |
Zuidinga, Birte [VerfasserIn] | |
Meijer, Marieke [VerfasserIn] | |
Russell, Robert B. [VerfasserIn] | |
Verhage, Matthijs [VerfasserIn] | |
Söllner, Thomas [VerfasserIn] | |
Titel: | The interaction of Munc18-1 helix 11 and 12 with the central region of the VAMP2 SNARE motif is essential for SNARE templating and synaptic transmission |
Verf.angabe: | Timon André, Jessica Classen, Philipp Brenner, Matthew J Betts, Bernhard Dörr, Susanne Kreye, Birte Zuidinga, Marieke Meijer, Robert B Russell, Matthijs Verhage, and Thomas H Söllner |
E-Jahr: | 2020 |
Jahr: | 14 October 2020 |
Fussnoten: | Gesehen am 18.01.2021 |
Titel Quelle: | Enthalten in: eNeuro |
Ort Quelle: | Washington, DC : Soc., 2014 |
Jahr Quelle: | 2020 |
Band/Heft Quelle: | 7(2020,6) Artikel-Nummer 0278-20.2020, 15 Seiten |
ISSN Quelle: | 2373-2822 |
Abstract: | Sec1/Munc18 proteins play a key role in initiating the assembly of N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes, the molecular fusion machinery. Employing comparative structure modeling, site specific crosslinking by single amino acid substitutions with the photoactivatable unnatural amino acid p-Benzoyl-phenylalanine (Bpa) and reconstituted vesicle docking/fusion assays, we mapped the binding interface between Munc18-1 and the neuronal v-SNARE VAMP2 with single amino acid resolution. Our results show that helices 11 and 12 of domain 3a in Munc18-1 interact with the VAMP2 SNARE motif covering the region from layers À4 to 15. Residue Q301 in helix 11 plays a pivotal role in VAMP2 binding and template complex formation. A VAMP2 binding deficient mutant, Munc18-1 Q301D, does not stimulate lipid mixing in a reconstituted fusion assay. The neuronal SNARE-organizer Munc13-1, which also binds VAMP2, does not bypass the requirement for the Munc18-1·VAMP2 interaction. Importantly, Munc18-1 Q301D expression in Munc18-1 deficient neurons severely reduces synaptic transmission, demonstrating the physiological significance of the Munc18-1·VAMP2 interaction. |
DOI: | doi:10.1523/ENEURO.0278-20.2020 |
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/10.1523/ENEURO.0278-20.2020 |
DOI: https://doi.org/10.1523/ENEURO.0278-20.2020 | |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1744885028 |
Verknüpfungen: | → Zeitschrift |