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 | Herausgeber: | eLIFE SCIENCES PUBL LTD | Journal: | ELIFE | Volumen: | 11 | Zusammenfassung: | 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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geprüft am 13.05.2024