2obd
Crystal Structure of Cholesteryl Ester Transfer Protein
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: CETP deficiency OMIM:[118470], Hyperalphalipoproteinemia OMIM:[118470], Longevity, exceptional OMIM:[118470]
About this StructureAbout this Structure
2OBD is a Single protein structure of sequence from Homo sapiens with CL, 2OB, PCW, EPE, 1PE and PG4 as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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
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