| Structural highlights
Function
[PEP5_YEAST] Required for vacuolar biogenesis and for trafficking of hydrolase precursors to the vacuole. Mediates transport at the vacuolar membrane where it may be responsible for tethering transport vesicles on the target membranes. It is required for gluconeogenic growth of yeast. Acts as component of the HOPS complex that acts during the docking stage of vacuole fusion. HOPS is an effector for the vacuolar Rab GTPase YPT7 and is required for vacuolar SNARE complex assembly. It remains bound to SNARE complexes after vacuole fusion (PubMed:3062374, PubMed:10978279, PubMed:10944212, PubMed:16601699). Acts as component of the CORVET complex that is required for transport between endosome and vacuole. CORVET is an effector for the endosomal Rab GTPase VPS21 (PubMed:17488625). Probable ubiquitin-protein ligase involved in the degradation-related ubiquitination of histones. Contributes to the post-translational regulation of histone protein levels by polyubiquitination of excess histones for subsequent degradation (PubMed:22570702).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
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.
Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery.,Shvarev D, Schoppe J, Konig C, Perz A, Fullbrunn N, Kiontke S, Langemeyer L, Januliene D, Schnelle K, Kummel D, Frohlich F, Moeller A, Ungermann C Elife. 2022 Sep 13;11. pii: 80901. doi: 10.7554/eLife.80901. PMID:36098503[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Seals DF, Eitzen G, Margolis N, Wickner WT, Price A. A Ypt/Rab effector complex containing the Sec1 homolog Vps33p is required for homotypic vacuole fusion. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9402-7. doi:, 10.1073/pnas.97.17.9402. PMID:10944212 doi:http://dx.doi.org/10.1073/pnas.97.17.9402
- ↑ Srivastava A, Woolford CA, Jones EW. Pep3p/Pep5p complex: a putative docking factor at multiple steps of vesicular transport to the vacuole of Saccharomyces cerevisiae. Genetics. 2000 Sep;156(1):105-22. PMID:10978279
- ↑ Stroupe C, Collins KM, Fratti RA, Wickner W. Purification of active HOPS complex reveals its affinities for phosphoinositides and the SNARE Vam7p. EMBO J. 2006 Apr 19;25(8):1579-89. Epub 2006 Apr 6. PMID:16601699 doi:http://dx.doi.org/7601051
- ↑ Peplowska K, Markgraf DF, Ostrowicz CW, Bange G, Ungermann C. The CORVET tethering complex interacts with the yeast Rab5 homolog Vps21 and is involved in endo-lysosomal biogenesis. Dev Cell. 2007 May;12(5):739-50. doi: 10.1016/j.devcel.2007.03.006. PMID:17488625 doi:http://dx.doi.org/10.1016/j.devcel.2007.03.006
- ↑ Singh RK, Gonzalez M, Kabbaj MH, Gunjan A. Novel E3 ubiquitin ligases that regulate histone protein levels in the budding yeast Saccharomyces cerevisiae. PLoS One. 2012;7(5):e36295. doi: 10.1371/journal.pone.0036295. Epub 2012 May 3. PMID:22570702 doi:http://dx.doi.org/10.1371/journal.pone.0036295
- ↑ Robinson JS, Klionsky DJ, Banta LM, Emr SD. Protein sorting in Saccharomyces cerevisiae: isolation of mutants defective in the delivery and processing of multiple vacuolar hydrolases. Mol Cell Biol. 1988 Nov;8(11):4936-48. PMID:3062374
- ↑ Shvarev D, Schoppe J, Konig C, Perz A, Fullbrunn N, Kiontke S, Langemeyer L, Januliene D, Schnelle K, Kummel D, Frohlich F, Moeller A, Ungermann C. Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery. Elife. 2022 Sep 13;11. pii: 80901. doi: 10.7554/eLife.80901. PMID:36098503 doi:http://dx.doi.org/10.7554/eLife.80901
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