Sec18 binds the tethering/SM complex HOPS to engage the Qc-SNARE for membrane fusion
1Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755-3844.
Molecular Biology of the Cell
|March 27, 2024
Summary
Sec18 (NSF) directly binds HOPS to restore membrane fusion at low HOPS levels. This Sec17-independent function enhances Qc-SNARE engagement, crucial for efficient fusion.
Area of Science:
- Cell biology
- Membrane trafficking
- Protein-protein interactions
Background:
- Membrane fusion relies on Rab GTPases, HOPS tethering factors, SNAREs, SM proteins, Sec17 (SNAP), and Sec18 (NSF).
- HOPS can mediate fusion at high concentrations without Sec18.
Purpose of the Study:
- Investigate the role of Sec18 at limiting HOPS concentrations.
- Elucidate the mechanism by which Sec18 influences HOPS-mediated fusion.
Main Methods:
- In vitro membrane fusion assays.
- Quantification of SNARE complex assembly and disassembly.
- Analysis of Sec18-HOPS interactions.
Main Results:
- Fusion efficiency decreases significantly at low HOPS levels.
- Direct Sec18 binding to HOPS restores fusion in a Sec17-independent manner, requiring adenine nucleotide.
- Sec18 enhances HOPS recognition of the Qc-SNARE, lowering its Km for fusion.
- Sec18 and HOPS concentration do not affect Qb-SNARE recognition.
Conclusions:
- A novel Sec17-independent function of Sec18 is identified: direct binding to HOPS.
- This interaction enhances functional Qc-SNARE engagement, critical for efficient membrane fusion.
- Sec18 plays a multifaceted role in membrane fusion beyond SNARE complex disassembly.
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