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Cited by 13Cellular transport and secretionExtracellular vesicles in diseaseMicrotubule and mitosis dynamics

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Structure of a membrane tethering complex incorporating multiple SNAREs

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DAmico, Kevin A., Stanton, Abigail E., Shirkey, Jaden D., Travis, Sophie M., Jeffrey, Philip D., Hughson, Frederick M.·2024·Nature Structural & Molecular Biology
DOI 10.1038/s41594-023-01164-8PMC PMC10923073

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Abstract

Most membrane fusion reactions in eukaryotic cells are mediated by multisubunit tethering complexes (MTCs) and SNARE proteins. MTCs are much larger than SNAREs and are thought to mediate the initial attachment of two membranes. Complementary SNAREs then form membrane-bridging complexes whose assembly draws the membranes together for fusion. Here we present a cryo-electron microscopy structure of the simplest known MTC, the 255-kDa Dsl1 complex of Saccharomyces cerevisiae, bound to the two SNAREs that anchor it to the endoplasmic reticulum. N-terminal domains of the SNAREs form an integral part of the structure, stabilizing a Dsl1 complex configuration with unexpected similarities to the 850-kDa exocyst MTC. The structure of the SNARE-anchored Dsl1 complex and its comparison with exocyst reveal what are likely to be common principles underlying MTC function. Our structure also implies that tethers and SNAREs can work together as a single integrated machine.

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Metadata

Authors
DAmico, K. A., Stanton, A. E., Shirkey, J. D., Travis, S. M., Jeffrey, P. D., & Hughson, F. M.
Affiliations
Princeton University (US)
Corresponding author
Hughson, Frederick M.
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2024-01-09
Volume
31
Issue
2
Pages
246-254
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-023-01164-8
PMC
PMC10923073
OpenAlex
W4390707028
Cited by
13
References
1
Citations by year
2026: 3 · 2025: 6 · 2024: 2
FWCI
2.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • National Science Foundation (2011750)
  • Princeton University (DMR-2011750)
  • Princeton Center for Complex Materials (DMR-2011750)
  • National Institutes of Health
  • Materials Research Science and Engineering Center, Harvard University (DMR2011750)
  • National Institute of General Medical Sciences (T32GM007388, R01GM071574)
  • Division of Materials Research (DMR2011750, 2011750)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
SNARE proteins, exocyst, membrane fusion, vesicle trafficking, endoplasmic reticulum, Saccharomyces cerevisiae, transport vesicles

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