Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery
- Osnabrück University, Germany
- Philipp University of Marburg, Germany
- University of Münster, Germany
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.
Data availability
All diffraction data are deposited in the PDB as indicated in the manuscript. PDB files are mentioned there.
Article and author information
Author details
Christian Ungermann
Funding
Deutsche Forschungsgemeinschaft (SFB 944,P11)
- Christian Ungermann
Deutsche Forschungsgemeinschaft (SFB 944,P27)
- Arne Moeller
Deutsche Forschungsgemeinschaft (SFB 944,P20)
- Florian Fröhlich
Deutsche Forschungsgemeinschaft (UN111/5-6)
- Arne Moeller
- Christian Ungermann
Deutsche Forschungsgemeinschaft (INST190/196-1 FUGG)
- Arne Moeller
Bundesministerium fur Bildung und Forschung (BMBF/DLR 01ED2010)
- Arne Moeller
Deutsche Forschungsgemeinschaft (SFB 944,P16)
- Daniel Kümmel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Benjamin S Glick, The University of Chicago, United States
Version history
- Preprint posted: May 5, 2022 (view preprint)
- Received: June 8, 2022
- Accepted: September 12, 2022
- Accepted Manuscript published: September 13, 2022 (version 1)
- Version of Record published: October 21, 2022 (version 2)
Copyright
© 2022, Shvarev et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery
eLife 11:e80901.
https://doi.org/10.7554/eLife.80901
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