Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
André, T; Classen, J; Brenner, P; Betts, MJ; Dörr, B; Kreye, S; Zuidinga, B; Meijer, M; Russell, RB; Verhage, M; Söllner, TH.
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.
eNeuro. 2020; 7(6):
Doi: 10.1523/ENEURO.0278-20.2020
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PubMed
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- Co-Autor*innen der Med Uni Graz
- Zuidinga Birte
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- 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 -4 to +5. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Membrane Fusion - administration & dosage
- Munc18 Proteins - genetics, metabolism
- Protein Binding - administration & dosage
- Rats - administration & dosage
- SNARE Proteins - genetics, metabolism
- Synaptic Transmission - administration & dosage
- Vesicle-Associated Membrane Protein 2 - genetics, metabolism