SNARE Zippering Is Suppressed by a Conformational Constraint that Is Removed by v-SNARE Splitting
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 co...
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Veröffentlicht in: | Cell reports (Cambridge) 2021-01, Vol.34 (2), p.108611-108611, Article 108611 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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•A conformational constraint of SNAREs is removed by v-SNARE splitting•Split SNARE-driven fusion mimics the SM protein-activated fusion reaction•v-SNARE splitting enables efficient trans-SNARE zippering•Split SNARE-driven fusion lacks compartmental specificity
SNAREs are unable to drive efficient membrane fusion unless activated by Sec1/Munc18 (SM) proteins. In this work, Liu et al. demonstrate that v-SNARE splitting mimics SM protein activation and unleashes the full membrane fusion potential of SNAREs. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2020.108611 |