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

Autor(en): Shvarev, Dmitry
Schoppe, Jannis
Koenig, Caroline
Perz, Angela
Fuellbrunn, Nadia
Kiontke, Stephan
Langemeyer, Lars
Januliene, Dovile 
Schnelle, Kilian
Kuemmel, Daniel 
Froehlich, Florian 
Moeller, Arne 
Ungermann, Christian 
Stichwörter: Biology; cerevisiae; CORVET; CRYO-EM; FINGER PROTEIN; HIGH-ACCURACY; HOPS; Life Sciences & Biomedicine - Other Topics; lysosome; membrane fusion; MOLECULAR ARCHITECTURE; MULTIPLE SEQUENCE ALIGNMENT; Rab GTPase; RAB INTERACTIONS; REQUIRES; S; SNARE COMPLEX; tethering; vacuole; VACUOLE FUSION
Erscheinungsdatum: 2022
Journal: ELIFE
Volumen: 11
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.
ISSN: 2050-084X
DOI: 10.7554/eLife.80901

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