SNARE Zippering Is Suppressed by a Conformational Constraint that Is Removed by v-SNARE Splitting.
SM protein
SNARE
membrane fusion
vesicle fusion
vesicle fusion specificity
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
12 01 2021
12 01 2021
Historique:
received:
10
09
2020
revised:
18
11
2020
accepted:
16
12
2020
entrez:
13
1
2021
pubmed:
14
1
2021
medline:
5
1
2022
Statut:
ppublish
Résumé
Intracellular vesicle fusion is catalyzed by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Vesicle-anchored v-SNAREs pair with target membrane-associated t-SNAREs to form trans-SNARE complexes, releasing free energy to drive membrane fusion. However, trans-SNARE complexes are unable to assemble efficiently unless activated by Sec1/Munc18 (SM) proteins. Here, we demonstrate that SNAREs become fully active when the v-SNARE is split into two fragments, eliminating the requirement of SM protein activation. Mechanistically, v-SNARE splitting accelerates the zippering of trans-SNARE complexes, mimicking the stimulatory function of SM proteins. Thus, SNAREs possess the full potential to drive efficient membrane fusion but are suppressed by a conformational constraint. This constraint is removed by SM protein activation or v-SNARE splitting. We suggest that ancestral SNAREs originally evolved to be fully active in the absence of SM proteins. Later, a conformational constraint coevolved with SM proteins to achieve the vesicle fusion specificity demanded by complex endomembrane systems.
Identifiants
pubmed: 33440145
pii: S2211-1247(20)31600-4
doi: 10.1016/j.celrep.2020.108611
pmc: PMC7837384
mid: NIHMS1662660
pii:
doi:
Substances chimiques
SNARE Proteins
0
Vesicular Transport Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108611Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK124431
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM126960
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061829
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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