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Cited by 85Cellular transport and secretionAutophagy in Disease and TherapyCalcium signaling and nucleotide metabolism

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Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery

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Shvarev, Dmitry, Schoppe, Jannis, König, Caroline, Perz, Angela, Füllbrunn, Nadia, Kiontke, Stephan, Langemeyer, Lars, Januliene, Dovile, Schnelle, Kilian, Kümmel, Daniel, Fröhlich, Florian, Moeller, Arne, Ungermann, Christian·2022·eLife
DOI 10.7554/elife.80901PMC PMC9592082

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Abstract

Lysosomes are essential for cellular recycling, nutrient signaling, autophagy, and pathogenic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requires HOPS, a conserved heterohexameric tethering complex. On the membranes to be fused, HOPS binds small membrane-associated GTPases and assembles SNAREs for fusion, but how the complex fulfills its function remained speculative. Here, we used cryo-electron microscopy to reveal the structure of HOPS. Unlike previously reported, significant flexibility of HOPS is confined to its extremities, where GTPase binding occurs. The SNARE-binding module is firmly attached to the core, therefore, ideally positioned between the membranes to catalyze fusion. Our data suggest a model for how HOPS fulfills its dual functionality of tethering and fusion and indicate why it is an essential part of the membrane fusion machinery.

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Metadata

Authors
Shvarev, D., Schoppe, J., König, C., Perz, A., Füllbrunn, N., Kiontke, S., Langemeyer, L., Januliene, D., Schnelle, K., Kümmel, D., Fröhlich, F., Moeller, A., & Ungermann, C.
Affiliations
  • Osnabrück University (DE)
  • Philipps University of Marburg (DE)
  • University of Münster (DE)
Corresponding author
  • Moeller, Arne
  • Ungermann, Christian
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-09-13
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.80901
PMC
PMC9592082
OpenAlex
W4295366884
Cited by
85
References
4
Citations by year
2026: 12 · 2025: 27 · 2024: 24 · 2023: 17 · 2022: 5
FWCI
9.74
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
Funders
  • Deutsche Forschungsgemeinschaft (UN111/5-6, INST190/196-1 FUGG, SFB 944 P11, SFB 944 P27, SFB 944 P20, SFB 944 P16, MO 2752/3-6)
  • Bundesministerium für Bildung und Forschung (BMBF/DLR 01ED2010)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
protein complex structure, membrane tethering, autophagy, lysosomes
MeSH terms
Lysosomes, Membrane Fusion, Saccharomyces cerevisiae, Vacuoles, Cryoelectron Microscopy, rab GTP-Binding Proteins, Saccharomyces cerevisiae Proteins, SNARE Proteins

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