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

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 dramatical...

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Main Authors: Lu Ma, Yuhao Kang, Junyi Jiao, Aleksander A. Rebane, Hyo Keun Cha, Zhiqun Xi, Hong Qu, Yongli Zhang
Format: Article
Language:English
Published: Elsevier 2016-04-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124716303217
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spelling doaj-4208b9f7419140b883c7f46f504fa1622020-11-24T21:21:04ZengElsevierCell Reports2211-12472016-04-0115353153910.1016/j.celrep.2016.03.050α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix BundleLu Ma0Yuhao Kang1Junyi Jiao2Aleksander A. Rebane3Hyo Keun Cha4Zhiqun Xi5Hong Qu6Yongli Zhang7Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USAIntracellular 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.http://www.sciencedirect.com/science/article/pii/S2211124716303217
collection DOAJ
language English
format Article
sources DOAJ
author Lu Ma
Yuhao Kang
Junyi Jiao
Aleksander A. Rebane
Hyo Keun Cha
Zhiqun Xi
Hong Qu
Yongli Zhang
spellingShingle Lu Ma
Yuhao Kang
Junyi Jiao
Aleksander A. Rebane
Hyo Keun Cha
Zhiqun Xi
Hong Qu
Yongli Zhang
α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle
Cell Reports
author_facet Lu Ma
Yuhao Kang
Junyi Jiao
Aleksander A. Rebane
Hyo Keun Cha
Zhiqun Xi
Hong Qu
Yongli Zhang
author_sort Lu Ma
title α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle
title_short α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle
title_full α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle
title_fullStr α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle
title_full_unstemmed α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle
title_sort α-snap enhances snare zippering by stabilizing the snare four-helix bundle
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2016-04-01
description 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.
url http://www.sciencedirect.com/science/article/pii/S2211124716303217
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