2obd
From Proteopedia
(New page: 200px<br /> <applet load="2obd" size="450" color="white" frame="true" align="right" spinBox="true" caption="2obd, resolution 2.10Å" /> '''Crystal Structure o...) |
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| - | [[Image:2obd.gif|left|200px]]<br /> | + | [[Image:2obd.gif|left|200px]]<br /><applet load="2obd" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2obd, resolution 2.10Å" /> | caption="2obd, resolution 2.10Å" /> | ||
'''Crystal Structure of Cholesteryl Ester Transfer Protein'''<br /> | '''Crystal Structure of Cholesteryl Ester Transfer Protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cholesteryl ester transfer protein (CETP) shuttles various lipids between | + | Cholesteryl ester transfer protein (CETP) shuttles various lipids between lipoproteins, resulting in the net transfer of cholesteryl esters from atheroprotective, high-density lipoproteins (HDL) to atherogenic, lower-density species. Inhibition of CETP raises HDL cholesterol and may potentially be used to treat cardiovascular disease. Here we describe the structure of CETP at 2.2-A resolution, revealing a 60-A-long tunnel filled with two hydrophobic cholesteryl esters and plugged by an amphiphilic phosphatidylcholine at each end. The two tunnel openings are large enough to allow lipid access, which is aided by a flexible helix and possibly also by a mobile flap. The curvature of the concave surface of CETP matches the radius of curvature of HDL particles, and potential conformational changes may occur to accommodate larger lipoprotein particles. Point mutations blocking the middle of the tunnel abolish lipid-transfer activities, suggesting that neutral lipids pass through this continuous tunnel. |
==Disease== | ==Disease== | ||
| - | Known diseases associated with this structure: CETP deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], Hyperalphalipoproteinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], Longevity, exceptional OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]] | + | Known diseases associated with this structure: CETP deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], High density lipoprotein cholesterol level QTL 10 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], Hyperalphalipoproteinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]], Longevity, exceptional OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=118470 118470]] |
==About this Structure== | ==About this Structure== | ||
| - | 2OBD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL, 2OB, PCW, EPE, 1PE and PG4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2OBD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=2OB:'>2OB</scene>, <scene name='pdbligand=PCW:'>PCW</scene>, <scene name='pdbligand=EPE:'>EPE</scene>, <scene name='pdbligand=1PE:'>1PE</scene> and <scene name='pdbligand=PG4:'>PG4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OBD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: lipid transfer protein]] | [[Category: lipid transfer protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:16:32 2008'' |
Revision as of 16:16, 21 February 2008
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Crystal Structure of Cholesteryl Ester Transfer Protein
Contents |
Overview
Cholesteryl ester transfer protein (CETP) shuttles various lipids between lipoproteins, resulting in the net transfer of cholesteryl esters from atheroprotective, high-density lipoproteins (HDL) to atherogenic, lower-density species. Inhibition of CETP raises HDL cholesterol and may potentially be used to treat cardiovascular disease. Here we describe the structure of CETP at 2.2-A resolution, revealing a 60-A-long tunnel filled with two hydrophobic cholesteryl esters and plugged by an amphiphilic phosphatidylcholine at each end. The two tunnel openings are large enough to allow lipid access, which is aided by a flexible helix and possibly also by a mobile flap. The curvature of the concave surface of CETP matches the radius of curvature of HDL particles, and potential conformational changes may occur to accommodate larger lipoprotein particles. Point mutations blocking the middle of the tunnel abolish lipid-transfer activities, suggesting that neutral lipids pass through this continuous tunnel.
Disease
Known diseases associated with this structure: CETP deficiency OMIM:[118470], High density lipoprotein cholesterol level QTL 10 OMIM:[118470], Hyperalphalipoproteinemia OMIM:[118470], Longevity, exceptional OMIM:[118470]
About this Structure
2OBD is a Single protein structure of sequence from Homo sapiens with , , , , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules., Qiu X, Mistry A, Ammirati MJ, Chrunyk BA, Clark RW, Cong Y, Culp JS, Danley DE, Freeman TB, Geoghegan KF, Griffor MC, Hawrylik SJ, Hayward CM, Hensley P, Hoth LR, Karam GA, Lira ME, Lloyd DB, McGrath KM, Stutzman-Engwall KJ, Subashi AK, Subashi TA, Thompson JF, Wang IK, Zhao H, Seddon AP, Nat Struct Mol Biol. 2007 Feb;14(2):106-13. Epub 2007 Jan 21. PMID:17237796
Page seeded by OCA on Thu Feb 21 18:16:32 2008
Categories: Homo sapiens | Single protein | Qiu, X. | 1PE | 2OB | CL | EPE | PCW | PG4 | Cholesteryl ester | Lipid transfer protein
