5zm8

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of ORP2-ORD in complex with PI(4,5)P2

Structural highlights

5zm8 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

OSBL2_HUMAN Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry.

Function

OSBL2_HUMAN Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate (PubMed:11279184). Binds 25-hydroxycholesterol (PubMed:17428193).^[1] ^[2]

Publication Abstract from PubMed

Cholesterol is highly enriched at the plasma membrane (PM), and lipid transfer proteins may deliver cholesterol to the PM in a nonvesicular manner. Here, through a mini-screen, we identified the oxysterol binding protein (OSBP)-related protein 2 (ORP2) as a novel mediator of selective cholesterol delivery to the PM. Interestingly, ORP2-mediated enrichment of PM cholesterol was coupled with the removal of phosphatidylinositol 4, 5-bisphosphate (PI(4,5)P2) from the PM. ORP2 overexpression or deficiency impacted the levels of PM cholesterol and PI(4,5)P2, and ORP2 efficiently transferred both cholesterol and PI(4,5)P2in vitro. We determined the structure of ORP2 in complex with PI(4,5)P2 at 2.7 A resolution. ORP2 formed a stable tetramer in the presence of PI(4,5)P2, and tetramerization was required for ORP2 to transfer PI(4,5)P2. Our results identify a novel pathway for cholesterol delivery to the PM and establish ORP2 as a key regulator of both cholesterol and PI(4,5)P2 of the PM.

ORP2 Delivers Cholesterol to the Plasma Membrane in Exchange for Phosphatidylinositol 4, 5-Bisphosphate (PI(4,5)P2).,Wang H, Ma Q, Qi Y, Dong J, Du X, Rae J, Wang J, Wu WF, Brown AJ, Parton RG, Wu JW, Yang H Mol Cell. 2018 Dec 10. pii: S1097-2765(18)30984-5. doi:, 10.1016/j.molcel.2018.11.014. PMID:30581148^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xu Y, Liu Y, Ridgway ND, McMaster CR. Novel members of the human oxysterol-binding protein family bind phospholipids and regulate vesicle transport. J Biol Chem. 2001 May 25;276(21):18407-14. Epub 2001 Feb 26. PMID:11279184 doi:http://dx.doi.org/10.1074/jbc.M101204200
↑ Suchanek M, Hynynen R, Wohlfahrt G, Lehto M, Johansson M, Saarinen H, Radzikowska A, Thiele C, Olkkonen VM. The mammalian oxysterol-binding protein-related proteins (ORPs) bind 25-hydroxycholesterol in an evolutionarily conserved pocket. Biochem J. 2007 Aug 1;405(3):473-80. PMID:17428193 doi:http://dx.doi.org/10.1042/BJ20070176
↑ Wang H, Ma Q, Qi Y, Dong J, Du X, Rae J, Wang J, Wu WF, Brown AJ, Parton RG, Wu JW, Yang H. ORP2 Delivers Cholesterol to the Plasma Membrane in Exchange for Phosphatidylinositol 4, 5-Bisphosphate (PI(4,5)P2). Mol Cell. 2018 Dec 10. pii: S1097-2765(18)30984-5. doi:, 10.1016/j.molcel.2018.11.014. PMID:30581148 doi:http://dx.doi.org/10.1016/j.molcel.2018.11.014

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5zm8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of ORP2-ORD in complex with PI(4,5)P2==
-<StructureSection load='5zm8' size='340' side='right' caption='[[5zm8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='5zm8' size='340' side='right'caption='[[5zm8]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5zm8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZM8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZM8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5zm8]] 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=5ZM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZM8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.7&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5zm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zm8 OCA], [http://pdbe.org/5zm8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zm8 RCSB], [http://www.ebi.ac.uk/pdbsum/5zm8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zm8 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=5zm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zm8 OCA], [https://pdbe.org/5zm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zm8 RCSB], [https://www.ebi.ac.uk/pdbsum/5zm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zm8 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/OSBL2_HUMAN OSBL2_HUMAN]] Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/OSBL2_HUMAN OSBL2_HUMAN] Autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/OSBL2_HUMAN OSBL2_HUMAN]] Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate (PubMed:11279184). Binds 25-hydroxycholesterol (PubMed:17428193).<ref>PMID:11279184</ref> <ref>PMID:17428193</ref>
+[https://www.uniprot.org/uniprot/OSBL2_HUMAN OSBL2_HUMAN] Binds phospholipids; exhibits strong binding to phosphatidic acid and weak binding to phosphatidylinositol 3-phosphate (PubMed:11279184). Binds 25-hydroxycholesterol (PubMed:17428193).<ref>PMID:11279184</ref> <ref>PMID:17428193</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Dong, J Q]]
+[[Category: Homo sapiens]]
-[[Category: Wang, H]]
+[[Category: Large Structures]]
-[[Category: Wang, J]]
+[[Category: Dong JQ]]
-[[Category: Wu, J W]]
+[[Category: Wang H]]
-[[Category: Complex]]
+[[Category: Wang J]]
-[[Category: Lipid transport]]
+[[Category: Wu JW]]
-[[Category: Phospholipid]]
-[[Category: Transporter]]

5zm8

From Proteopedia

Current revision

Crystal structure of ORP2-ORD in complex with PI(4,5)P2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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