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bioRxiv · 10.1101/2021.02.16.431494

Sec17/Sec18 can support membrane fusion without help from completion of SNARE zippering

Song, H.·Torng, T. L.·Orr, A.·Brunger, A. T.·Wickner, W. T.
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Abstract

Membrane fusion requires R-, Qa-, Qb-, and Qc-family SNAREs that zipper into RQaQbQc coiled coils, driven by the sequestration of apolar amino acids. Zippering has been thought to provide all the force driving fusion. Sec17/SNAP can form an oligomeric assembly with SNAREs with the Sec17 C-terminus bound to Sec18/NSF, the central region bound to SNAREs, and a crucial apolar loop near the N-terminus poised to insert into membranes. Though Sec17 aids zippering, we now report that Sec17 and Sec18 will drive robust fusion without requiring zippering completion. Zippering-driven fusion is blocked by deleting the C-terminal quarter of any Q-SNARE domain or by replacing the apolar amino acids of the Qa-SNARE which face the center of the 4-SNARE coiled coils with polar residues. These blocks to fusion, singly or combined, are bypassed by Sec17 and Sec18, and SNARE-dependent fusion is restored without help from completing zippering.

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Song, H., Torng, T. L., Orr, A., Brunger, A. T., Wickner, W. T.. 2021-02-17. Sec17/Sec18 can support membrane fusion without help from completion of SNARE zippering. https://doi.org/10.1101/2021.02.16.431494

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