Sandbox 215: Difference between revisions

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===Four lipid binding sites===

CETP's structure reveals a 60 Å long hydrophobic tunnel which traverses the core of the molecule and contains four lipid binding sites: two neutral lipids binding sites in the middle of the tunnel and two phospholipids binding sites (one at each end). The center of the tunnel which is called the “neck” is 10 Å wide and 5 Å high that is large enough to permit the passage of neutral lipid.

A wall of ß-sheets underneath the lipids and a layer of helices above the lipids forms the longest tunnel that it exists in lipid-binding and lipid-transfer protein.

Cholesteryl ester 1 (CE1) is situated between the N barrel and the central ß-sheet. This binding site is mostly composed of hydrophobic residues and only a few polar. CE1 is too far away from the Ser 230 to establish a hydrogen bond but CE1 can establish some π-starking interaction.

Cholesteryl ester 2 penetrates deeper into the barrel than CE1 and resides between the central ß-sheet and the C-barrel. This site contains even fewer polar groups than CE1 binding site. That's why CE2 is not able to make any hydrogen-bonding or π-starking interaction.

The N-opening of the tunnel is 10 Å wide and 5 Å high whereas the C-opening is 13 Å X 5 Å. The C-opening is a little bit larger but both are large enough to allow lipid access.

Each opening of the tunnel is plugged by one phospholipid which buries its hydrophobic acyl chain inside the tunnel and its hydrophilic head groups to the solvent.

'''Helix X and Ω flaps'''

Some mobile structures located near tunnel openings facilitate the lipid transfer.

The helix X belongs to the C-terminal domain and thanks to its Gly462-Phe463-Pro464 groupment is flexible. It is an amphiphathic helix. 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 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 from lipoprotein to CETP.

Near the C-opening, there are also two Ω flaps: Ω1 and Ω2. These flaps are linked through the 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. Ω1 also plays an important role.

Sandbox 215: Difference between revisions

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@@ Line 23: / Line 23: @@
 ===Four lipid binding sites===
+CETP's structure reveals a 60 Å long hydrophobic tunnel which traverses the core of the molecule and contains four lipid binding sites: two neutral lipids binding sites in the middle of the tunnel and two phospholipids binding sites (one at each end). The center of the tunnel which is called the “neck” is 10 Å wide and 5 Å high that is large enough to permit the passage of neutral lipid.
+A wall of ß-sheets underneath the lipids and a layer of helices above the lipids forms the longest tunnel that it exists in lipid-binding and lipid-transfer protein.
+Cholesteryl ester 1 (CE1) is situated between the N barrel and the central ß-sheet. This binding site is mostly composed of hydrophobic residues and only a few polar. CE1 is too far away from the Ser 230 to establish a hydrogen bond but CE1 can establish some π-starking interaction.
+Cholesteryl ester 2 penetrates deeper into the barrel than CE1 and resides between the central ß-sheet and the C-barrel. This site contains even fewer polar groups than CE1 binding site. That's why CE2 is not able to make any hydrogen-bonding or π-starking interaction.
+The N-opening of the tunnel is 10 Å wide and 5 Å high whereas the C-opening is 13 Å X 5 Å. The C-opening is a little bit larger but both are large enough to allow lipid access.
+Each opening of the tunnel is plugged by one phospholipid which buries its hydrophobic acyl chain inside the tunnel and its hydrophilic head groups to the solvent.
+'''Helix X and Ω flaps'''
+Some mobile structures located near tunnel openings facilitate the lipid transfer.
+The helix X belongs to the C-terminal domain and thanks to its Gly462-Phe463-Pro464 groupment is flexible. It is an amphiphathic helix. 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 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 from lipoprotein to CETP.
+Near the C-opening, there are also two Ω flaps:  Ω1 and  Ω2. These flaps are linked through the 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. Ω1  also plays an important role.