SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18
Secretory and endolysosomal fusion events are driven by SNAREs and cofactors, including Sec17/α-SNAP, Sec18/NSF, and Sec1/Munc18 (SM) proteins. SMs are essential for fusion in vivo, but the basis of this requirement is enigmatic. We now report that, in addition to their established roles as fusion a...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/02272 |
| _version_ | 1818018914368487424 |
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| author | Braden T Lobingier Daniel P Nickerson Sheng-Ying Lo Alexey J Merz |
| author_facet | Braden T Lobingier Daniel P Nickerson Sheng-Ying Lo Alexey J Merz |
| author_sort | Braden T Lobingier |
| collection | DOAJ |
| description | Secretory and endolysosomal fusion events are driven by SNAREs and cofactors, including Sec17/α-SNAP, Sec18/NSF, and Sec1/Munc18 (SM) proteins. SMs are essential for fusion in vivo, but the basis of this requirement is enigmatic. We now report that, in addition to their established roles as fusion accelerators, SM proteins Sly1 and Vps33 directly shield SNARE complexes from Sec17- and Sec18-mediated disassembly. In vivo, wild-type Sly1 and Vps33 function are required to withstand overproduction of Sec17. In vitro, Sly1 and Vps33 impede SNARE complex disassembly by Sec18 and ATP. Unexpectedly, Sec17 directly promotes selective loading of Sly1 and Vps33 onto cognate SNARE complexes. A large thermodynamic barrier limits SM binding, implying that significant conformational rearrangements are involved. In a working model, Sec17 and SMs accelerate fusion mediated by cognate SNARE complexes and protect them from NSF-mediated disassembly, while mis-assembled or non-cognate SNARE complexes are eliminated through kinetic proofreading by Sec18. |
| first_indexed | 2024-04-14T07:45:52Z |
| format | Article |
| id | doaj.art-37bf2c9442994b53942e5c05f6ea59b8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:45:52Z |
| publishDate | 2014-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-37bf2c9442994b53942e5c05f6ea59b82022-12-22T02:05:20ZengeLife Sciences Publications LtdeLife2050-084X2014-05-01310.7554/eLife.02272SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18Braden T Lobingier0Daniel P Nickerson1Sheng-Ying Lo2Alexey J Merz3Department of Biochemistry, University of Washington School of Medicine, Seattle, United StatesDepartment of Biochemistry, University of Washington School of Medicine, Seattle, United StatesDepartment of Biochemistry, University of Washington School of Medicine, Seattle, United StatesDepartment of Biochemistry, University of Washington School of Medicine, Seattle, United States; Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, United StatesSecretory and endolysosomal fusion events are driven by SNAREs and cofactors, including Sec17/α-SNAP, Sec18/NSF, and Sec1/Munc18 (SM) proteins. SMs are essential for fusion in vivo, but the basis of this requirement is enigmatic. We now report that, in addition to their established roles as fusion accelerators, SM proteins Sly1 and Vps33 directly shield SNARE complexes from Sec17- and Sec18-mediated disassembly. In vivo, wild-type Sly1 and Vps33 function are required to withstand overproduction of Sec17. In vitro, Sly1 and Vps33 impede SNARE complex disassembly by Sec18 and ATP. Unexpectedly, Sec17 directly promotes selective loading of Sly1 and Vps33 onto cognate SNARE complexes. A large thermodynamic barrier limits SM binding, implying that significant conformational rearrangements are involved. In a working model, Sec17 and SMs accelerate fusion mediated by cognate SNARE complexes and protect them from NSF-mediated disassembly, while mis-assembled or non-cognate SNARE complexes are eliminated through kinetic proofreading by Sec18.https://elifesciences.org/articles/02272membraneSNAREdockingHOPSlysosomeGolgi |
| spellingShingle | Braden T Lobingier Daniel P Nickerson Sheng-Ying Lo Alexey J Merz SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18 eLife membrane SNARE docking HOPS lysosome Golgi |
| title | SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18 |
| title_full | SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18 |
| title_fullStr | SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18 |
| title_full_unstemmed | SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18 |
| title_short | SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18 |
| title_sort | sm proteins sly1 and vps33 co assemble with sec17 and snare complexes to oppose snare disassembly by sec18 |
| topic | membrane SNARE docking HOPS lysosome Golgi |
| url | https://elifesciences.org/articles/02272 |
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