Sandbox 215: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
|||
| Line 2: | Line 2: | ||
{{STRUCTURE_2obd| PDB=2obd | SCENE= }} | {{STRUCTURE_2obd| PDB=2obd | SCENE= }} | ||
[http://en.wikipedia.org/wiki/Cholesterylester_transfer_protein Cholesteryl ester transfer protein (CETP)], which is also called plasma lipid transfer protein belongs to a family of proteins that | [http://en.wikipedia.org/wiki/Cholesterylester_transfer_protein Cholesteryl ester transfer protein (CETP)], which is also called plasma lipid transfer protein belongs to a family of proteins that allow lipid transfer. The [http://en.wikipedia.org/wiki/Homo_sapiens human] cholesteryl ester transfer protein is a hydrophobic glycoprotein which is mainly synthesized in the liver, but also in the intestine, spleen and adrenal glands. The gene coding for this protein is located on the sixteen chromosome. | ||
In the plasma, CETP plays an important role in the transport of cholesteryl esters from the atheroprotective high-density lipoproteins (HDL) to the atherogenic lower-density lipoproteins (LDL) and also mediates the transport of triglycerides from LDL to HDL. | In the plasma, CETP plays an important role in the transport of cholesteryl esters from the atheroprotective high-density lipoproteins (HDL) to the atherogenic lower-density lipoproteins (LDL) and also mediates the transport of triglycerides from LDL to HDL. | ||
Most of the time, CETP facilites homoexchange by exchanging a triglyceride for another triglyceride and a cholesteryl ester for a cholesteryl ester between lipoproteins. However, CETP can also | Most of the time, CETP facilites homoexchange by exchanging a triglyceride for another triglyceride and a cholesteryl ester for a cholesteryl ester between lipoproteins. However, CETP can also promote heteroexchange. | ||
The cristal structure of CETP, in complex with four bound lipid molecules at 2, | The cristal structure of CETP, in complex with four bound lipid molecules at 2,2 Å resolution shows a long tunnel traversing the core of the molecule. This tunnel has two large openings allowing lipids access and each opening is plugged by an amphiphilic phosphatidylcholine. | ||
| Line 51: | Line 51: | ||
The amphiphathic <scene name='Sandbox_215/Helix_x/1'>helix X</scene> which belongs to the C-terminal domain is flexible thanks to her | The amphiphathic <scene name='Sandbox_215/Helix_x/1'>helix X</scene> which belongs to the C-terminal domain is flexible thanks to her | ||
<scene name='Sandbox_215/Gly462-phe463-pro464/1'>Gly462-Phe463-Pro464</scene> groupment. The hydrophobic face of helix X interacts with phosphatidylcholine 1 located at the N-terminal in order to form an apolar path allowing the access of neutral lipids to the tunnel. Mutations on the hydrophobic face of helix X reduce transfer activities whereas mutations on the polar side do not have any effects on transfer activities. These results prove that helix X plays an important role in transferring neutral lipid between lipoproteins. | <scene name='Sandbox_215/Gly462-phe463-pro464/1'>Gly462-Phe463-Pro464</scene> groupment. The hydrophobic face of helix X interacts with phosphatidylcholine 1 located at the N-terminal in order to form an apolar path allowing the access of neutral lipids to the tunnel. Mutations on the hydrophobic face of helix X reduce transfer activities whereas mutations on the polar side do not have any effects on transfer activities. These results prove that helix X plays an important role in transferring neutral lipid between lipoproteins. | ||
Near the C-opening, there are also two Ω flaps: Ω1 and Ω2. These flaps are linked through a starking interaction between the Phe292 and Ph350. The flap Ω1 interacts with the oleoyl tail of the cholesteryl ester 2 in order to protect the lipid from aqueous solvent exposure and also to help the exchange of lipids through the C opening.</StructureSection> | Near the C-opening, there are also two Ω flaps: Ω1 and Ω2. These flaps are linked through a starking interaction between the Phe292 and Ph350. The flap Ω1 interacts with the oleoyl tail of the cholesteryl ester 2 in order to protect the lipid from aqueous solvent exposure and also to help the exchange of lipids through the C opening.</StructureSection> | ||
