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

Autor:	Caroline König, Jannis Schoppe, Dmitry Shvarev, Angela Perz, Nadia Füllbrunn, Stephan Kiontke, Lars Langemeyer, Dovile Januliene, Kilian Schnelle, Daniel Kümmel, Florian Fröhlich, Arne Moeller, Christian Ungermann
Rok vydání:	2022
Předmět:	Saccharomyces cerevisiae Proteins General Immunology and Microbiology General Neuroscience Cryoelectron Microscopy Saccharomyces cerevisiae General Medicine Membrane Fusion General Biochemistry Genetics and Molecular Biology rab GTP-Binding Proteins Vacuoles SNARE Proteins Lysosomes ddc:600
Zdroj:	eLife 11, e80901 (2022). doi:10.7554/eLife.80901
ISSN:	2050-084X
Popis:	eLife 11, e80901 (2022). doi:10.7554/eLife.80901 Lysosomes are essential for cellular recycling, nutrient signaling, autophagy, and patho-genic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requiresHOPS, a conserved heterohexameric tethering complex. On the membranes to be fused, HOPSbinds small membrane- associated GTPases and assembles SNAREs for fusion, but how the complexfulfills its function remained speculative. Here, we used cryo-electron microscopy to reveal the struc-ture 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 howHOPS fulfills its dual functionality of tethering and fusion and indicate why it is an essential part ofthe membrane fusion machinery. Published by eLife Sciences Publications, Cambridge
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5cdbb1f3709575f8990ebf950ccab91 https://doi.org/10.7554/elife.80901 Zobrazit plný text záznamu