| Structural highlights
5h2c is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Related: | 5h2d, 5h28, 5h2a |
| Gene: | SWH1, OSH1, YAR042W, YAR044W (Baker's yeast), NVJ1, VAB36, YHR195W (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[OSH1_YEAST] Lipid-binding protein involved in maintenance of intracellular sterol distribution and homeostasis. Binds to phosphoinositides. May be involved in formation of PMN vesicles by altering the membrane lipid composition.[1] [NVJ1_YEAST] Involved in the formation of nucleus-vacuole (NV) junctions during piecemeal microautophagy of the nucleus (PMN). NV junctions are interorganelle interfaces mediated by NVJ1 in the nuclear envelope and VAC8 on the vacuole membrane. Together, NVJ1 and VAC8 form Velcro-like patches through which teardrop-like portions of the nucleus are pinched off into the vacuolar lumen and degraded by the PMN process. Acts also as an outer-nuclear membrane receptor for OSH1 and TSC13.[2] [3] [4] [5] [6]
Publication Abstract from PubMed
Yeast Osh1 belongs to the oxysterol-binding protein (OSBP) family of proteins and contains multiple targeting modules optimized for lipid transport at the nucleus-vacuole junction (NVJ). The key determinants for NVJ targeting and the role of Osh1 at NVJs have remained elusive because of unknown lipid specificities. In this study, we determined the structures of the ankyrin repeat domain (ANK), and OSBP-related domain (ORD) of Osh1, in complex with Nvj1 and ergosterol, respectively. The Osh1 ANK forms a unique bi-lobed structure that recognizes a cytosolic helical segment of Nvj1. We discovered that Osh1 ORD binds ergosterol and phosphatidylinositol 4-phosphate PI(4)P in a competitive manner, suggesting counter-transport function of the two lipids. Ergosterol is bound to the hydrophobic pocket in a head-down orientation, and the structure of the PI(4)P-binding site in Osh1 is well conserved. Our results suggest that Osh1 performs non-vesicular transport of ergosterol and PI(4)P at the NVJ.
Structure of Yeast OSBP-Related Protein Osh1 Reveals Key Determinants for Lipid Transport and Protein Targeting at the Nucleus-Vacuole Junction.,Manik MK, Yang H, Tong J, Im YJ Structure. 2017 Apr 4;25(4):617-629.e3. doi: 10.1016/j.str.2017.02.010. Epub 2017, Mar 16. PMID:28319008[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Beh CT, Rine J. A role for yeast oxysterol-binding protein homologs in endocytosis and in the maintenance of intracellular sterol-lipid distribution. J Cell Sci. 2004 Jun 15;117(Pt 14):2983-96. Epub 2004 Jun 1. PMID:15173322 doi:http://dx.doi.org/10.1242/jcs.01157
- ↑ Pan X, Roberts P, Chen Y, Kvam E, Shulga N, Huang K, Lemmon S, Goldfarb DS. Nucleus-vacuole junctions in Saccharomyces cerevisiae are formed through the direct interaction of Vac8p with Nvj1p. Mol Biol Cell. 2000 Jul;11(7):2445-57. PMID:10888680
- ↑ Roberts P, Moshitch-Moshkovitz S, Kvam E, O'Toole E, Winey M, Goldfarb DS. Piecemeal microautophagy of nucleus in Saccharomyces cerevisiae. Mol Biol Cell. 2003 Jan;14(1):129-41. PMID:12529432 doi:http://dx.doi.org/10.1091/mbc.E02-08-0483
- ↑ Kvam E, Goldfarb DS. Nvj1p is the outer-nuclear-membrane receptor for oxysterol-binding protein homolog Osh1p in Saccharomyces cerevisiae. J Cell Sci. 2004 Oct 1;117(Pt 21):4959-68. Epub 2004 Sep 14. PMID:15367582 doi:http://dx.doi.org/10.1242/jcs.01372
- ↑ Kvam E, Gable K, Dunn TM, Goldfarb DS. Targeting of Tsc13p to nucleus-vacuole junctions: a role for very-long-chain fatty acids in the biogenesis of microautophagic vesicles. Mol Biol Cell. 2005 Sep;16(9):3987-98. Epub 2005 Jun 15. PMID:15958487 doi:http://dx.doi.org/10.1091/mbc.E05-04-0290
- ↑ Kvam E, Goldfarb DS. Structure and function of nucleus-vacuole junctions: outer-nuclear-membrane targeting of Nvj1p and a role in tryptophan uptake. J Cell Sci. 2006 Sep 1;119(Pt 17):3622-33. Epub 2006 Aug 15. PMID:16912077 doi:http://dx.doi.org/10.1242/jcs.03093
- ↑ Manik MK, Yang H, Tong J, Im YJ. Structure of Yeast OSBP-Related Protein Osh1 Reveals Key Determinants for Lipid Transport and Protein Targeting at the Nucleus-Vacuole Junction. Structure. 2017 Apr 4;25(4):617-629.e3. doi: 10.1016/j.str.2017.02.010. Epub 2017, Mar 16. PMID:28319008 doi:http://dx.doi.org/10.1016/j.str.2017.02.010
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