5zm6
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==Crystal structure of ORP1-ORD in complex with PI(4,5)P2== | ==Crystal structure of ORP1-ORD in complex with PI(4,5)P2== | ||
| - | <StructureSection load='5zm6' size='340' side='right' caption='[[5zm6]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='5zm6' size='340' side='right'caption='[[5zm6]], [[Resolution|resolution]] 2.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5zm6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZM6 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5zm6]] 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=5ZM6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZM6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IEP:[(2~{S})-1-octadecanoyloxy-3-[oxidanyl-[(1~{R},2~{R},3~{S},4~{S},5~{S},6~{S})-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propan-2-yl]+icosa-5,8,11,14-tetraenoate'>IEP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=IEP:[(2~{S})-1-octadecanoyloxy-3-[oxidanyl-[(1~{R},2~{R},3~{S},4~{S},5~{S},6~{S})-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propan-2-yl]+icosa-5,8,11,14-tetraenoate'>IEP</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=5zm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zm6 OCA], [https://pdbe.org/5zm6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zm6 RCSB], [https://www.ebi.ac.uk/pdbsum/5zm6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zm6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/OSBL1_HUMAN OSBL1_HUMAN] Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate (By similarity). Stabilizes GTP-bound RAB7A on late endosomes/lysosomes and alters functional properties of late endocytic compartments via its interaction with RAB7A (PubMed:16176980). Binds 25-hydroxycholesterol and cholesterol (PubMed:17428193).<ref>PMID:16176980</ref> <ref>PMID:17428193</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Phosphatidylinositol phosphates (PIPs) and cholesterol are known to regulate the function of late endosomes and lysosomes (LELs), and ORP1L specifically localizes to LELs. Here, we show in vitro that ORP1 is a PI(4,5)P2- or PI(3,4)P2-dependent cholesterol transporter, but cannot transport any PIPs. In cells, both ORP1L and PI(3,4)P2 are required for the efficient removal of cholesterol from LELs. Structures of the lipid-binding domain of ORP1 (ORP1-ORD) in complex with cholesterol or PI(4,5)P2 display open conformations essential for ORP function. PI(4,5)P2/PI(3,4)P2 can facilitate ORP1-mediated cholesterol transport by promoting membrane targeting and cholesterol extraction. Thus, our work unveils a distinct mechanism by which PIPs may allosterically enhance OSBP/ORPs-mediated transport of major lipid species such as cholesterol. | ||
| + | |||
| + | Allosteric enhancement of ORP1-mediated cholesterol transport by PI(4,5)P2/PI(3,4)P2.,Dong J, Du X, Wang H, Wang J, Lu C, Chen X, Zhu Z, Luo Z, Yu L, Brown AJ, Yang H, Wu JW Nat Commun. 2019 Feb 19;10(1):829. doi: 10.1038/s41467-019-08791-0. PMID:30783101<ref>PMID:30783101</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5zm6" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Dong J]] |
| - | [[Category: | + | [[Category: Luo Z]] |
| - | [[Category: | + | [[Category: Wang J]] |
| - | [[Category: | + | [[Category: Wu JW]] |
| - | + | ||
| - | + | ||
Current revision
Crystal structure of ORP1-ORD in complex with PI(4,5)P2
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Categories: Homo sapiens | Large Structures | Dong J | Luo Z | Wang J | Wu JW
