2obd

From Proteopedia

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Revision as of 16:42, 19 January 2015

Crystal Structure of Cholesteryl Ester Transfer Protein

Structural highlights

2obd is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , ,
Gene:	CETP (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[CETP_HUMAN] Defects in CETP are the cause of hyperalphalipoproteinemia type 1 (HALP1) [MIM:143470]. Affected individuals show high levels of alpha-lipoprotein (high density lipoprotein/HDL).^[1] ^[2] ^[3]

Function

[CETP_HUMAN] Involved in the transfer of insoluble cholesteryl esters in the reverse transport of cholesterol.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[4]

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

References

↑ Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, Maruhama Y, Mabuchi H, Tall AR. Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med. 1990 Nov 1;323(18):1234-8. PMID:2215607 doi:http://dx.doi.org/10.1056/NEJM199011013231803
↑ Takahashi K, Jiang XC, Sakai N, Yamashita S, Hirano K, Bujo H, Yamazaki H, Kusunoki J, Miura T, Kussie P, et al.. A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins. J Clin Invest. 1993 Oct;92(4):2060-4. PMID:8408659 doi:http://dx.doi.org/10.1172/JCI116802
↑ Nagano M, Yamashita S, Hirano K, Ito M, Maruyama T, Ishihara M, Sagehashi Y, Oka T, Kujiraoka T, Hattori H, Nakajima N, Egashira T, Kondo M, Sakai N, Matsuzawa Y. Two novel missense mutations in the CETP gene in Japanese hyperalphalipoproteinemic subjects: high-throughput assay by Invader assay. J Lipid Res. 2002 Jul;43(7):1011-8. PMID:12091484
↑ 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. Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules. Nat Struct Mol Biol. 2007 Feb;14(2):106-13. Epub 2007 Jan 21. PMID:17237796 doi:10.1038/nsmb1197