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PDB:2OBD

Protein Name

Cholesterol ester transfer protein

Species

Human

Biological Context

Cholesterol is an essential component for cell membrane and hormone synthesis. but if it exists to excess, cholesterol clots in the blood vessel and subsequently causes cardiovascular diseases. Therefore, systemic cholesterol homeostasis is vital for our good health.

Cholesterol homeostasis is regulated by some transfer proteins named lipoproteins. Some lipoproteins bind to cholesterol and shuttle between liver and other peripheral tissues. High density lipoprotein (HDL), called “good cholesterol”, removes excess cholesterol from peripheral tissues and delivers it to liver. In the liver, the cholesterol bound to HDL is transferred to very low density lipoprotein (VLDL). VLDL is converted to low density lipoprotein (LDL) in the blood and supplies cholesterol to the peripheral tissues. Because excess LDL increases the cholesterol amount in the peripheral tissues, LDL is called “bad cholesterol”.

The protein described here, cholesterol ester transfer protein (CETP), catalyzes the exchange of cholesterol between HDL and VLDL.

Structure Description

2obd2obd_x2obd_y

CETP has an elongated boomerang shape with dimensions of 135 Å×30 Å×35 Å. The structure of CETP can be divided into four structural units: one barrel including a highly twisted β sheet and two α helices at each end of the protein (barrels N and C), a six-antiparallel stranded β sheet between two barrels, a linker, and C terminal helix X. 60 Å long hydrophobic tunnel that can hold four lipids traverses the core of the protein (fig1, 2). In this structure, two cholesteryl esters are buried in the tunnel and two phospholipids plug the each opening of the tunnel. Flexible helix X and mobile flip Ω1 in the C terminal barrel locate near the two openings respectively, and would aid lipid access and exclusion. The structure described here is considered the HDL binding form because curvature of the concave surface of CETP matches the radius of the HDL particle (fig2). Conformational changes would occur when accommodating larger VLDL particles.

fig1
fig1. Overall structure of CETP
Choresteril esters and phospholipids are colored as purple and white respectively.
fig2
fig2. Surface structure of CRTP
As shown with dotted line, the concave surface of CETP matches the radius of the HDL particle.

Protein Data Bank (PDB)

References

Source

Qiu, X. Mistry, A. Ammirati, M.J. Chrunyk, B.A. Clark, R.W. Cong, Y. Culp, J.S. Danley, D.E. Freeman, T.B. Geoghegan, K.F. Griffor, M.C. Hawrylik, S.J. Hayward, C.M. Hensley, P. Hoth, L.R. Karam, G.A. Lira, M.E. Lloyd, D.B. McGrath, K.M. Stutzman-Engwall, K.J. Subashi, A.K. Subashi, T.A. Thompson, J.F. Wang, I.K. Zhao, H. Seddon, A.P.; "Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules."; Nat.Struct.Mol.Biol.; (2007) 14:106-113 PubMed:17237796.

Others

author: Daisuke Ino


Japanese version:PDB:2OBD