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| | <StructureSection load='5dfz' size='340' side='right'caption='[[5dfz]], [[Resolution|resolution]] 4.40Å' scene=''> | | <StructureSection load='5dfz' size='340' side='right'caption='[[5dfz]], [[Resolution|resolution]] 4.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dfz]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824], [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast] and [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DFZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DFZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dfz]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama], [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DFZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DFZ FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5dfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfz OCA], [https://pdbe.org/5dfz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dfz RCSB], [https://www.ebi.ac.uk/pdbsum/5dfz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dfz ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VPS38, VPL17, YLR360W, L8039.11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), VPS34, END12, PEP15, VPL7, VPT29, YLR240W, L9672.10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), VPS15, GRD8, VAC4, VPL19, YBR097W, YBR0825 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast]), VPS30, APG6, ATG6, VPT30, YPL120W, LPH7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dfz OCA], [http://pdbe.org/5dfz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dfz RCSB], [http://www.ebi.ac.uk/pdbsum/5dfz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dfz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/VPS38_YEAST VPS38_YEAST]] Involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through generating a specific pool of phosphatidylinositol 3-phosphate allowing the recruitment of the retromer complex proteins to the endosome). Mediates the interaction between VPS30 and the VPS34-VPS15 core complex, leading to the recruitment of VPS30 to the membrane.<ref>PMID:11157979</ref> <ref>PMID:12244127</ref> <ref>PMID:9265642</ref> [[http://www.uniprot.org/uniprot/VPS15_YEAST VPS15_YEAST]] Serine/threonine-protein kinase required for cytoplasm to vacuole transport (Cvt) and autophagy as a part of the autophagy-specific VPS34 PI3-kinase complex I. This complex is essential to recruit the ATG8-phosphatidylinositol conjugate and the ATG12-ATG5 conjugate to the pre-autophagosomal structure. Is also involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This second complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through the synthesis of a specific pool of phosphatidylinositol 3-phosphate recruiting the retromer to the endosomes). By regulating VPS34 kinase activity, VPS15 appears to be essential for the efficient delivery of soluble hydrolases to the yeast vacuole.<ref>PMID:1988155</ref> <ref>PMID:3062374</ref> <ref>PMID:1756716</ref> <ref>PMID:8387919</ref> <ref>PMID:8509446</ref> <ref>PMID:7989323</ref> <ref>PMID:8649377</ref> <ref>PMID:11157979</ref> <ref>PMID:12244127</ref> [[http://www.uniprot.org/uniprot/VPS34_YEAST VPS34_YEAST]] Phosphatidylinositol 3-kinase required for cytoplasm to vacuole transport (Cvt) and autophagy as a part of the autophagy-specific VPS34 PI3-kinase complex I. This complex is essential to recruit the ATG8-phosphatidylinositol conjugate and the ATG12-ATG5 conjugate to the pre-autophagosomal structure. Also involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This second complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through the synthesis of a specific pool of phosphatidylinositol 3-phosphate recruiting the retromer to the endosomes). Its activation by VPS15 may lead to the phosphorylation of phosphatidylinositol in the sorting compartment membrane. Finally, it might also be involved in ethanol tolerance and cell wall integrity.<ref>PMID:11157979</ref> <ref>PMID:11523784</ref> <ref>PMID:12244127</ref> <ref>PMID:2247081</ref> <ref>PMID:2555343</ref> <ref>PMID:3062374</ref> <ref>PMID:7929582</ref> <ref>PMID:7989323</ref> <ref>PMID:8385367</ref> <ref>PMID:8387919</ref> [[http://www.uniprot.org/uniprot/BECN1_YEAST BECN1_YEAST]] Required for cytoplasm to vacuole transport (Cvt), autophagy, nucleophagy, and mitophagy, as a part of the autophagy-specific VPS34 PI3-kinase complex I. This complex is essential to recruit the ATG8-phosphatidylinositol conjugate and the ATG12-ATG5 conjugate to the pre-autophagosomal structure. Also involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This second complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through the synthesis of a specific pool of phosphatidylinositol 3-phosphate recruiting the retromer to the endosomes). Plays also a role in regulation of filamentous growth.<ref>PMID:11157979</ref> <ref>PMID:11689437</ref> <ref>PMID:12244127</ref> <ref>PMID:16267277</ref> <ref>PMID:17404498</ref> <ref>PMID:17700056</ref> <ref>PMID:18182384</ref> <ref>PMID:18701704</ref> <ref>PMID:19131141</ref> <ref>PMID:22437838</ref> <ref>PMID:23878393</ref> <ref>PMID:8224160</ref> <ref>PMID:9105038</ref> <ref>PMID:9712845</ref> | + | [https://www.uniprot.org/uniprot/VPS38_YEAST VPS38_YEAST] Involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through generating a specific pool of phosphatidylinositol 3-phosphate allowing the recruitment of the retromer complex proteins to the endosome). Mediates the interaction between VPS30 and the VPS34-VPS15 core complex, leading to the recruitment of VPS30 to the membrane.<ref>PMID:11157979</ref> <ref>PMID:12244127</ref> <ref>PMID:9265642</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | + | [[Category: Lama glama]] |
| - | [[Category: Baker's yeast]]
| + | |
| - | [[Category: Camelus glama]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphatidylinositol 3-kinase]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Ohashi, Y]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Rostislavleva, K]] | + | [[Category: Ohashi Y]] |
| - | [[Category: Soler, N]] | + | [[Category: Rostislavleva K]] |
| - | [[Category: Williams, R L]] | + | [[Category: Soler N]] |
| - | [[Category: Zhang, L]] | + | [[Category: Williams RL]] |
| - | [[Category: Autophagy]]
| + | [[Category: Zhang L]] |
| - | [[Category: Bara]]
| + | |
| - | [[Category: C2]]
| + | |
| - | [[Category: Coiled-coil]]
| + | |
| - | [[Category: Complex ii]]
| + | |
| - | [[Category: Heat]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Lipid]]
| + | |
| - | [[Category: Nanobody]]
| + | |
| - | [[Category: Pi3p]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Vacuolar protein sorting]]
| + | |
| - | [[Category: Vps15]]
| + | |
| - | [[Category: Vps30]]
| + | |
| - | [[Category: Vps34]]
| + | |
| - | [[Category: Vps38]]
| + | |
| - | [[Category: Wd40]]
| + | |
| - | [[Category: Yeast]]
| + | |
| Structural highlights
Function
VPS38_YEAST Involved in endosome-to-Golgi retrograde transport as part of the VPS34 PI3-kinase complex II. This complex is required for the endosome-to-Golgi retrieval of PEP1 and KEX2, and the recruitment of VPS5 and VPS7, two components of the retromer complex, to endosomal membranes (probably through generating a specific pool of phosphatidylinositol 3-phosphate allowing the recruitment of the retromer complex proteins to the endosome). Mediates the interaction between VPS30 and the VPS34-VPS15 core complex, leading to the recruitment of VPS30 to the membrane.[1] [2] [3]
Publication Abstract from PubMed
Phosphatidylinositol 3-kinase Vps34 complexes regulate intracellular membrane trafficking in endocytic sorting, cytokinesis, and autophagy. We present the 4.4 angstrom crystal structure of the 385-kilodalton endosomal complex II (PIK3C3-CII), consisting of Vps34, Vps15 (p150), Vps30/Atg6 (Beclin 1), and Vps38 (UVRAG). The subunits form a Y-shaped complex, centered on the Vps34 C2 domain. Vps34 and Vps15 intertwine in one arm, where the Vps15 kinase domain engages the Vps34 activation loop to regulate its activity. Vps30 and Vps38 form the other arm that brackets the Vps15/Vps34 heterodimer, suggesting a path for complex assembly. We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to reveal conformational changes accompanying membrane binding and identify a Vps30 loop that is critical for the ability of complex II to phosphorylate giant liposomes on which complex I is inactive.
Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes.,Rostislavleva K, Soler N, Ohashi Y, Zhang L, Pardon E, Burke JE, Masson GR, Johnson C, Steyaert J, Ktistakis NT, Williams RL Science. 2015 Oct 9;350(6257):aac7365. doi: 10.1126/science.aac7365. PMID:26450213[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kihara A, Noda T, Ishihara N, Ohsumi Y. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol. 2001 Feb 5;152(3):519-30. PMID:11157979
- ↑ Burda P, Padilla SM, Sarkar S, Emr SD. Retromer function in endosome-to-Golgi retrograde transport is regulated by the yeast Vps34 PtdIns 3-kinase. J Cell Sci. 2002 Oct 15;115(Pt 20):3889-900. PMID:12244127
- ↑ Luo W, Chang A. Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant. J Cell Biol. 1997 Aug 25;138(4):731-46. PMID:9265642
- ↑ Rostislavleva K, Soler N, Ohashi Y, Zhang L, Pardon E, Burke JE, Masson GR, Johnson C, Steyaert J, Ktistakis NT, Williams RL. Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes. Science. 2015 Oct 9;350(6257):aac7365. doi: 10.1126/science.aac7365. PMID:26450213 doi:http://dx.doi.org/10.1126/science.aac7365
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