View source for 7dei


==Structure of human ORP3 ORD domain in complex with PI(4)P==
<StructureSection load='7dei' size='340' side='right'caption='[[7dei]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7dei]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DEI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PIF:(2R)-3-{[(S)-HYDROXY{[(1R,2R,3R,4R,5S,6R)-2,3,5,6-TETRAHYDROXY-4-(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}PROPANE-1,2-DIYL+DIOCTANOATE'>PIF</scene></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=7dei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dei OCA], [https://pdbe.org/7dei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dei RCSB], [https://www.ebi.ac.uk/pdbsum/7dei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dei ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OSBL3_HUMAN OSBL3_HUMAN] Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes (PubMed:16143324). Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:18270267, PubMed:25447204). With VAPA, may regulate ER morphology (PubMed:16143324). Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion (PubMed:18270267). Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3 (PubMed:16143324). Also binds 25-hydroxycholesterol and cholesterol (PubMed:17428193).<ref>PMID:16143324</ref> <ref>PMID:17428193</ref> <ref>PMID:18270267</ref> <ref>PMID:25447204</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human ORP3 belongs to the oxysterol-binding protein (OSBP) family of lipid transfer proteins and is involved in lipid trafficking and cell signaling. ORP3 localizes to the ER-PM interfaces and is implicated in lipid transport and focal adhesion dynamics. Here, we report the 2.6-2.7 A structures of the ORD (OSBP-related domain) of human ORP3 in apo-form and in complex with phosphatidylinositol 4-phosphate. The ORP3 ORD displays a helix grip beta-barrel fold with a deep hydrophobic pocket which is conserved in the OSBP gene family. ORP3 binds PI(4)P by the residues around tunnel entrance and in the hydrophobic pocket, whereas it lacks sterol binding due to the narrow hydrophobic tunnel. The heterologous expression of the ORDs of human ORP3 or OSBP1 rescued the lethality of seven ORP (yeast OSH1-OSH7) knockout in yeast. In contrast, the PI(4)P-binding site mutant of ORP3 did not complement the OSH knockout cells. The N-terminal PH domain and FFAT motif of ORP3 are involved in protein targeting but are not essential in yeast complementation. This observation suggests that the essential function conserved in the ORPs of yeast and human is mediated by PI(4)P-binding of the ORD domain. This study suggests that the non-vesicular PI(4)P transport is a conserved function of all ORPs in eukaryotes.

Structure of human ORP3 ORD reveals conservation of a key function and ligand specificity in OSBP-related proteins.,Tong J, Tan L, Im YJ PLoS One. 2021 Apr 15;16(4):e0248781. doi: 10.1371/journal.pone.0248781., eCollection 2021. PMID:33857182<ref>PMID:33857182</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dei" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Im YJ]]
[[Category: Tan L]]
[[Category: Tong J]]