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7v62

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Crystal structure of human OSBP ORD in complex with cholesterol

Structural highlights

7v62 is a 4 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 3.25Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OSBP1_HUMAN Binds cholesterol and a range of oxysterols. Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylate ERK1/2, whereas 25-hydroxycholesterol causes its disassembly. Regulates cholesterol efflux by decreasing ABCA1 stability.^[1] ^[2]

Publication Abstract from PubMed

Oxysterol-binding protein (OSBP), which transports cholesterol and phosphatidylinositol 4-monophosphate (PtdIns[4]P) between different organelles, serves as a conserved host factor for the replication of various viruses, and OSBP inhibitors exhibit antiviral effects. Here, we determined the crystal structure of the lipid transfer domain of human OSBP in complex with endogenous cholesterol. The hydrocarbon tail and tetracyclic ring of cholesterol interact with the hydrophobic tunnel of OSBP, and the hydroxyl group of cholesterol forms a hydrogen bond network at the bottom of the tunnel. Systematic mutagenesis of the ligand-binding region revealed that M446W and L590W substitutions confer functional tolerance to an OSBP inhibitor, T-00127-HEV2. Employing the M446W variant as a functional replacement for the endogenous OSBP in the presence of T-00127-HEV2, we have identified previously unappreciated amino acid residues required for viral replication. The combined use of the inhibitor and the OSBP variant will be useful in elucidating the enigmatic in vivo functions of OSBP.

Ligand Recognition by the Lipid Transfer Domain of Human OSBP Is Important for Enterovirus Replication.,Kobayashi J, Arita M, Sakai S, Kojima H, Senda M, Senda T, Hanada K, Kato R ACS Infect Dis. 2022 May 25. doi: 10.1021/acsinfecdis.2c00108. PMID:35613096^[3]

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

References

↑ Wang PY, Weng J, Anderson RG. OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science. 2005 Mar 4;307(5714):1472-6. PMID:15746430 doi:http://dx.doi.org/307/5714/1472
↑ Bowden K, Ridgway ND. OSBP negatively regulates ABCA1 protein stability. J Biol Chem. 2008 Jun 27;283(26):18210-7. Epub 2008 May 1. PMID:18450749 doi:http://dx.doi.org/M800918200
↑ Kobayashi J, Arita M, Sakai S, Kojima H, Senda M, Senda T, Hanada K, Kato R. Ligand Recognition by the Lipid Transfer Domain of Human OSBP Is Important for Enterovirus Replication. ACS Infect Dis. 2022 May 25. doi: 10.1021/acsinfecdis.2c00108. PMID:35613096 doi:http://dx.doi.org/10.1021/acsinfecdis.2c00108

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7v62"

Categories: Homo sapiens | Large Structures | Kato R | Kobayashi J

@@ Line 3: / Line 3: @@
 <StructureSection load='7v62' size='340' side='right'caption='[[7v62]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7v62]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7V62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V62 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7v62]] is a 4 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=7V62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V62 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</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]] 3.25&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</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=7v62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v62 OCA], [https://pdbe.org/7v62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v62 RCSB], [https://www.ebi.ac.uk/pdbsum/7v62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v62 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/OSBP1_HUMAN OSBP1_HUMAN]] Binds cholesterol and a range of oxysterols. Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylate ERK1/2, whereas 25-hydroxycholesterol causes its disassembly. Regulates cholesterol efflux by decreasing ABCA1 stability.<ref>PMID:15746430</ref> <ref>PMID:18450749</ref>
+[https://www.uniprot.org/uniprot/OSBP1_HUMAN OSBP1_HUMAN] Binds cholesterol and a range of oxysterols. Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylate ERK1/2, whereas 25-hydroxycholesterol causes its disassembly. Regulates cholesterol efflux by decreasing ABCA1 stability.<ref>PMID:15746430</ref> <ref>PMID:18450749</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Kato, R]]
+[[Category: Kato R]]
-[[Category: Kobayashi, J]]
+[[Category: Kobayashi J]]
-[[Category: Lipid binding protein]]
-[[Category: Lipid transport]]
-[[Category: Lipid transport protein]]
-[[Category: Oxysterol binding protein]]
-[[Category: Oxysterol binding protein-related domain]]

7v62

From Proteopedia

Current revision

Crystal structure of human OSBP ORD in complex with cholesterol

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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