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Cell Rep. 2016 Apr 19;15(3):531-539. doi: 10.1016/j.celrep.2016.03.050. Epub 2016 Apr 7.

α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle.

Author information

1
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA; Integrated Graduate Program in Physical and Engineering Biology, New Haven, CT 06520, USA.
3
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA; Integrated Graduate Program in Physical and Engineering Biology, New Haven, CT 06520, USA; Department of Physics, Yale University, New Haven, CT 06511, USA.
4
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: yongli.zhang@yale.edu.

Abstract

Intracellular membrane fusion is mediated by dynamic assembly and disassembly of soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors (SNAREs). α-SNAP guides NSF to disassemble SNARE complexes after membrane fusion. Recent experiments showed that α-SNAP also dramatically enhances SNARE assembly and membrane fusion. How α-SNAP is involved in these opposing activities is not known. Here, we examine the effect of α-SNAP on the stepwise assembly of the synaptic SNARE complex using optical tweezers. We found that α-SNAP destabilized the linker domain (LD) of the SNARE complex but stabilized its C-terminal domain (CTD) through a conformational selection mechanism. In contrast, α-SNAP minimally affected assembly of the SNARE N-terminal domain (NTD), indicating that α-SNAP barely bound the partially assembled trans-SNARE complex. Thus, α-SNAP recognizes the folded CTD for SNARE disassembly with NSF and subtly modulates membrane fusion by altering the stabilities of the SNARE CTD and LD.

PMID:
27068468
PMCID:
PMC4838522
DOI:
10.1016/j.celrep.2016.03.050
[Indexed for MEDLINE]
Free PMC Article

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