| Structural highlights
5xjg is a 4 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.
| | Ligands: | , |
| Gene: | VAC8, YEB3, YEL013W (Baker's yeast), NVJ1, VAB36, YHR195W (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[VAC8_YEAST] Functions in both vacuole inheritance and protein targeting from the cytoplasm to vacuole.[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
Formation of the nucleus-vacuole junction (NVJ) is mediated by direct interaction between the vacuolar protein Vac8p and the outer nuclear endoplasmic reticulum membrane protein Nvj1p. Herein we report the crystal structure of Vac8p bound to Nvj1p at 2.4-A resolution. Vac8p comprises a flexibly connected N-terminal H1 helix followed by 12 armadillo repeats (ARMs) that form a right-handed superhelical structure. The extended 80-A-long loop of Nvj1p specifically binds the highly conserved inner groove formed from ARM1-12 of Vac8p. Disruption of the Nvj1p-Vac8p interaction results in the loss of tight NVJs, which impairs piecemeal microautophagy of the nucleus in Saccharomyces cerevisiae Vac8p cationic triad (Arg276, Arg317, and Arg359) motifs interacting with Nvj1p are also critical to the recognition of Atg13p, a key component of the cytoplasm-to-vacuole targeting (CVT) pathway, indicating competitive binding to Vac8p. Indeed, mutation of the cationic triad abolishes CVT of Ape1p in vivo. Combined with biochemical data, the crystal structure reveals a Vac8p homodimer formed from ARM1, and this self-association, likely regulated by the flexible H1 helix and the C terminus of Nvj1p, is critical for Vac8p cellular functions.
Mechanistic insight into the nucleus-vacuole junction based on the Vac8p-Nvj1p crystal structure.,Jeong H, Park J, Kim HI, Lee M, Ko YJ, Lee S, Jun Y, Lee C Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):E4539-E4548. doi:, 10.1073/pnas.1701030114. Epub 2017 May 22. PMID:28533415[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang YX, Catlett NL, Weisman LS. Vac8p, a vacuolar protein with armadillo repeats, functions in both vacuole inheritance and protein targeting from the cytoplasm to vacuole. J Cell Biol. 1998 Mar 9;140(5):1063-74. PMID:9490720
- ↑ 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
- ↑ Jeong H, Park J, Kim HI, Lee M, Ko YJ, Lee S, Jun Y, Lee C. Mechanistic insight into the nucleus-vacuole junction based on the Vac8p-Nvj1p crystal structure. Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):E4539-E4548. doi:, 10.1073/pnas.1701030114. Epub 2017 May 22. PMID:28533415 doi:http://dx.doi.org/10.1073/pnas.1701030114
|
