View source for 5kc2


==Negative stain structure of Vps15/Vps34 complex==
<SX load='5kc2' size='340' side='right' viewer='molstar' caption='[[5kc2]], [[Resolution|resolution]] 28.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kc2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KC2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KC2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 28&#8491;</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=5kc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kc2 OCA], [https://pdbe.org/5kc2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kc2 RCSB], [https://www.ebi.ac.uk/pdbsum/5kc2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kc2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
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== Publication Abstract from PubMed ==
The phosphatidylinositol 3-kinase Vps34 is part of several protein complexes. The structural organization of heterotetrameric complexes is starting to emerge, but little is known about organization of additional accessory subunits that interact with these assemblies. Combining hydrogen-deuterium exchange mass spectrometry (HDX-MS), X-ray crystallography and electron microscopy (EM), we have characterized Atg38 and its human ortholog NRBF2, accessory components of complex I consisting of Vps15-Vps34-Vps30/Atg6-Atg14 (yeast) and PIK3R4/VPS15-PIK3C3/VPS34-BECN1/Beclin 1-ATG14 (human). HDX-MS shows that Atg38 binds the Vps30-Atg14 subcomplex of complex I, using mainly its N-terminal MIT domain and bridges the coiled-coil I regions of Atg14 and Vps30 in the base of complex I. The Atg38 C-terminal domain is important for localization to the phagophore assembly site (PAS) and homodimerization. Our 2.2 A resolution crystal structure of the Atg38 C-terminal homodimerization domain shows 2 segments of alpha-helices assembling into a mushroom-like asymmetric homodimer with a 4-helix cap and a parallel coiled-coil stalk. One Atg38 homodimer engages a single complex I. This is in sharp contrast to human NRBF2, which also forms a homodimer, but this homodimer can bridge 2 complex I assemblies.

Characterization of Atg38 and NRBF2, a fifth subunit of the autophagic Vps34/PIK3C3 complex.,Ohashi Y, Soler N, Garcia Ortegon M, Zhang L, Kirsten ML, Perisic O, Masson GR, Burke JE, Jakobi AJ, Apostolakis AA, Johnson CM, Ohashi M, Ktistakis NT, Sachse C, Williams RL Autophagy. 2016 Sep 14:0. PMID:27630019<ref>PMID:27630019</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5kc2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
*[[Vacuolar protein sorting-associated protein 3D structures|Vacuolar protein sorting-associated protein 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Kirsten ML]]
[[Category: Ohashi Y]]
[[Category: Perisic O]]
[[Category: Sachse C]]
[[Category: Williams RL]]
[[Category: Zhang L]]