Munc13 binds and recruits SNAP25 to chaperone SNARE complex assembly.
FEBS Lett
; 595(3): 297-309, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33222163
ABSTRACT
Synaptic vesicle fusion is mediated by SNARE proteins-VAMP2 on the vesicle and Syntaxin-1/SNAP25 on the presynaptic membrane. Chaperones Munc18-1 and Munc13-1 cooperatively catalyze SNARE assembly via an intermediate 'template' complex containing Syntaxin-1 and VAMP2. How SNAP25 enters this reaction remains a mystery. Here, we report that Munc13-1 recruits SNAP25 to initiate the ternary SNARE complex assembly by direct binding, as judged by bulk FRET spectroscopy and single-molecule optical tweezer studies. Detailed structure-function analyses show that the binding is mediated by the Munc13-1 MUN domain and is specific for the SNAP25 'linker' region that connects the two SNARE motifs. Consequently, freely diffusing SNAP25 molecules on phospholipid bilayers are concentrated and bound in ~ 1 1 stoichiometry by the self-assembled Munc13-1 nanoclusters.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sintaxina 1
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Proteína 25 Associada a Sinaptossoma
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Proteína 2 Associada à Membrana da Vesícula
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Lipossomos
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article