Structural principles of SNARE complex recognition by the AAA+ protein NSF

K Ian White; Minglei Zhao; Ucheor B Choi; Richard A Pfuetzner; Axel T Brunger

doi:10.7554/eLife.38888

eLife (Sep 2018)

Structural principles of SNARE complex recognition by the AAA+ protein NSF

K Ian White,
Minglei Zhao,
Ucheor B Choi,
Richard A Pfuetzner,
Axel T Brunger

Affiliations

K Ian White: ORCiD; Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States; Department of Structural Biology, Stanford University, Stanford, United States; Department of Photon Science, Stanford University, Stanford, United States; Howard Hughes Medical Institute, Stanford University, Stanford, United States
Minglei Zhao: ORCiD; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
Ucheor B Choi: ORCiD; Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States; Department of Structural Biology, Stanford University, Stanford, United States; Department of Photon Science, Stanford University, Stanford, United States; Howard Hughes Medical Institute, Stanford University, Stanford, United States
Richard A Pfuetzner: ORCiD; Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States; Department of Structural Biology, Stanford University, Stanford, United States; Department of Photon Science, Stanford University, Stanford, United States; Howard Hughes Medical Institute, Stanford University, Stanford, United States
Axel T Brunger: ORCiD; Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States; Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States; Department of Structural Biology, Stanford University, Stanford, United States; Department of Photon Science, Stanford University, Stanford, United States; Howard Hughes Medical Institute, Stanford University, Stanford, United States

DOI: https://doi.org/10.7554/eLife.38888
Journal volume & issue: Vol. 7

Abstract

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The recycling of SNARE proteins following complex formation and membrane fusion is an essential process in eukaryotic trafficking. A highly conserved AAA+ protein, NSF (N-ethylmaleimide sensitive factor) and an adaptor protein, SNAP (soluble NSF attachment protein), disassemble the SNARE complex. We report electron-cryomicroscopy structures of the complex of NSF, αSNAP, and the full-length soluble neuronal SNARE complex (composed of syntaxin-1A, synaptobrevin-2, SNAP-25A) in the presence of ATP under non-hydrolyzing conditions at ~3.9 Å resolution. These structures reveal electrostatic interactions by which two αSNAP molecules interface with a specific surface of the SNARE complex. This interaction positions the SNAREs such that the 15 N-terminal residues of SNAP-25A are loaded into the D1 ring pore of NSF via a spiral pattern of interactions between a conserved tyrosine NSF residue and SNAP-25A backbone atoms. This loading process likely precedes ATP hydrolysis. Subsequent ATP hydrolysis then drives complete disassembly.

Published in eLife

ISSN: 2050-084X (Online)
Publisher: eLife Sciences Publications Ltd
Country of publisher: United Kingdom
LCC subjects: Medicine; Science: Biology (General)
Website: https://elifesciences.org

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