Evidence map›Paper›PMID 39257774›Full record

ArticlebioRxiv : the preprint server for biology2025

SNARE disassembly requires Sec18/NSF side-loading.

Yousuf A Khan, K Ian White, Richard A Pfuetzner, Bharti Singal, Luis Esquivies, Garvey Mckenzie, Fang Liu, Katherine DeLong, Ucheor B Choi, Elizabeth Montabana and 3 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Yousuf A KhanDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-0201-2796
K Ian WhiteDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Richard A PfuetznerDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Bharti SingalStanford Cryo-EM microscopy center, Stanford University, Palo Alto, CA, USA.
Luis EsquiviesDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Garvey MckenzieStanford University Mass Spectrometry, Stanford University, Palo Alto, CA, USA.
Fang LiuStanford University Mass Spectrometry, Stanford University, Palo Alto, CA, USA.
Katherine DeLongDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Ucheor B ChoiDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Elizabeth MontabanaStanford Cryo-EM microscopy center, Stanford University, Palo Alto, CA, USA.
Theresa MclaughlinStanford University Mass Spectrometry, Stanford University, Palo Alto, CA, USA.
William T WicknerDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH 03755.
Axel T BrungerDepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-5121-2036

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
Mechanisms of Membrane FusionR35GM118037 · NIGMS · DARTMOUTH COLLEGE · PI WILLIAM Tobey WICKNER · 2016 to 2026
$8.6M
STRUCTURE OF PROTEINS INVOLVED IN SYNAPTIC EXOCYTOSISR01MH063105 · NIMH · STANFORD UNIVERSITY · PI BRUNGER, AXEL T · 2000 to 2025
$4.7M
A Modern Flexible Mass Spectrometry Platform for Advancing Proteomics ResearchS10OD030473 · OD · STANFORD UNIVERSITY · PI LEIB, RYAN D. · 2021 to 2021
$1.3M
Mechanistic Principles of SNARE Disassembly in Neurotransmitter ReleaseF31MH134477 · NIMH · STANFORD UNIVERSITY · PI KHAN, YOUSUF A · 2023 to 2025
$84k
NCI NIH HHS P30 CA124435NIGMS NIH HHS R35 GM118037NIH HHS S10 OD030473NIMH NIH HHS F31 MH134477NIMH NIH HHS R01 MH063105
6 · The paper itself

Abstract

SNARE proteins drive membrane fusion at different cell compartments as their core domains zipper into a parallel four-helix bundle. After fusion, these bundles are disassembled by the AAA+ protein Sec18/NSF and its adaptor Sec17/α-SNAP to make them available for subsequent rounds of membrane fusion. SNARE domains are often flanked by C-terminal transmembrane or N-terminal domains. Previous structures of the NSF-α-SNAP-SNARE complex revealed binding to the D1 ATPase pore, posing a topological constraint as SNARE transmembrane domains would prevent complete substrate threading as suggested for other AAA+ systems. Using mass-spectrometry in yeast cells, we show N-terminal SNARE domain interactions with Sec18, exacerbating this topological issue. We present cryo-EM structures of a yeast SNARE complex, Sec18, and Sec17 in a non-hydrolyzing condition, which show SNARE Sso1 threaded through the D1 and D2 ATPase rings of Sec18, with its folded, N-terminal Habc domain interacting with the D2 ring. This domain does not unfold during Sec18/NSF activity. Cryo-EM structures under hydrolyzing conditions revealed substrate-released and substrate-free states of Sec18 with a coordinated opening in the side of the ATPase rings. Thus, Sec18/NSF operates by substrate side-loading and unloading topologically constrained SNARE substrates.

Identifiers

PMID39257774
PMCPMC11384006

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.