Spring-loaded unraveling of a single SNARE complex by NSF in one round of ATP turnover

Ryu, Je-Kyung; Min, Duyoung; Rah, Sang-Hyun; Kim, Soo Jin; Park, Yong Soo; Kim, Haesoo; Hyeon, Changbong; Kim, Ho Min; Jahn, Reinhard; Yoon, Tae–Young

doi:10.1126/science.aaa5267

Cited by 78 publications

(84 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A hairpin structure inside the central pore has been demonstrated for other AAA ATPases, and there is even evidence that three strands can be present (Burton et al, 2001). This mechanism differs from that of NSF, where the SNARE substrate is not translocated through the central pore, although the D1 ring has canonical pore residues(Zhao et al, 2015), and a single ATPase cycle disassembles the SNARE complex (Ryu et al, 2015). …”

Section: Discussionmentioning

confidence: 97%

Molecular Mechanism of Substrate Processing by the Cdc48 ATPase Complex

Bodnar

Rapoport

2017

Cell

284

324

View full text Add to dashboard Cite

The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated proteins from membranes or macromolecular complexes, but how they perform these functions is unclear. Cdc48 consists of an N-terminal domain that binds UN and two stacked hexameric ATPase rings (D1 and D2) surrounding a central pore. Here, we use purified components to elucidate how the Cdc48 complex processes substrates. After interaction of the polyubiquitin chain with UN, ATP hydrolysis by the D2 ring moves the polypeptide completely through the double ring, generating a pulling force on the substrate and causing its unfolding. ATP hydrolysis by the D1 ring is important for subsequent substrate release from the Cdc48 complex. This release requires cooperation of Cdc48 with a deubiquitinase, which trims polyubiquitin to an oligoubiquitin chain that is then also translocated through the pore. Together, these results lead to a new paradigm for the function of Cdc48 and its mammalian ortholog p97/VCP.

show abstract

Section: Discussionmentioning

confidence: 97%

Molecular Mechanism of Substrate Processing by the Cdc48 ATPase Complex

Bodnar

Rapoport

2017

Cell

284

324

View full text Add to dashboard Cite

show abstract

“…NSF is a vesicle-fusing ATPase that binds SNARE complexes to separate them during ATP hydrolysis and disassembly of the SNARE complex (87). The PDZ-binding motif takes the form -(D/E)(S/T)X, where X is promiscuous and is a hydrophobic residue.…”

Section: Discussionmentioning

confidence: 99%

Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling

McGarvey¹,

Xiao²,

Bowman³

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

The G protein-coupled parathyroid hormone receptor (PTHR) regulates mineral-ion homeostasis and bone remodeling. Upon parathyroid hormone (PTH) stimulation, the PTHR internalizes into early endosomes and subsequently traffics to the retromer complex, a sorting platform on early endosomes that promotes recycling of surface receptors. The C terminus of the PTHR contains a type I PDZ ligand that binds PDZ domaincontaining proteins. Mass spectrometry identified sorting nexin 27 (SNX27) in isolated endosomes as a PTHR binding partner. PTH treatment enriched endosomal PTHR. SNX27 contains a PDZ domain and serves as a cargo selector for the retromer complex. VPS26, VPS29, and VPS35 retromer subunits were isolated with PTHR in endosomes from cells stimulated with PTH. Molecular dynamics and protein binding studies establish that PTHR and SNX27 interactions depend on the PDZ recognition motif in PTHR and the PDZ domain of SNX27. Depletion of either SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling following agonist stimulation. Mutating the PDZ ligand of PTHR abolished the interaction with SNX27 but did not affect the overall rate of recycling, suggesting that PTHR may directly engage the retromer complex. Coimmunoprecipitation and overlay experiments show that both intact and mutated PTHR bind retromer through the VPS26 protomer and sequentially assemble a ternary complex with PTHR and SNX27. SNX27-independent recycling may involve N-ethylmaleimide-sensitive factor, which binds both PDZ intact and mutant PTHRs. We conclude that PTHR recycles rapidly through at least two pathways, one involving the ASRT complex of actin, SNX27, and retromer and another possibly involving N-ethylmaleimide-sensitive factor.

show abstract

“…Park et al found that α-SNAP arrests the trans-SNARE complex in a half-zippered state, thereby preventing fusion in a membrane curvature-dependent manner (Park et al, 2014). Ryu et al observed that α-SNAP destabilizes the C-terminus of the SNARE complex but not enough to form the half-zippered state (Ryu et al, 2015). In contrast, Zick et al found that the yeast α-SNAP homologue, Sec17, strongly promotes trans-SNARE folding and triggers membrane fusion (Zick et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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

Kang

Jiao

et al. 2016

Cell Reports

View full text Add to dashboard Cite

Summary 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 plays roles in these opposing activities is not known. Here, we examined the effect of α-SNAP on the step-wise 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.

show abstract

Spring-loaded unraveling of a single SNARE complex by NSF in one round of ATP turnover

Cited by 78 publications

References 67 publications

Molecular Mechanism of Substrate Processing by the Cdc48 ATPase Complex

Molecular Mechanism of Substrate Processing by the Cdc48 ATPase Complex

Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling

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

Contact Info

Product

Resources

About