Sandbox 215: Difference between revisions
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CETP is a 476 amino acid residues protein which has an elongated “boomerang shape” with dimensions of 135 Å X 30 Å X 35 Å. She has a molecular mass of 74 kDa. CETP is a highly hydrophobic and glycosylated protein. In fact 28% of her mass is attributed to N-glycosylated residues : <scene name='Sandbox_215/N-glycosylation/3'>88, 240, 341 and 396</scene>. | CETP is a 476 amino acid residues protein which has an elongated “boomerang shape” with dimensions of 135 Å X 30 Å X 35 Å. She has a molecular mass of 74 kDa. CETP is a highly hydrophobic and glycosylated protein. In fact 28% of her mass is attributed to N-glycosylated residues : <scene name='Sandbox_215/N-glycosylation/3'>88, 240, 341 and 396</scene>. | ||
CETP is constitued of four structural units: <ref>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. Nature Structural & Molecular Biology. 2007 Feb;14(2):106-13. Epub 2007 Jan 21. [http://www.ncbi.nlm.nih.gov/pubmed?term=17237796. PMID: 17237796] [http://www.nature.com.scd-rproxy.u-strasbg.fr/nsmb/journal/v14/n2/full/nsmb1197.html doi:10.1038/nsmb1197]</ref> | CETP is constitued of four structural units: <ref name="Qiu">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. Nature Structural & Molecular Biology. 2007 Feb;14(2):106-13. Epub 2007 Jan 21. [http://www.ncbi.nlm.nih.gov/pubmed?term=17237796. PMID: 17237796] [http://www.nature.com.scd-rproxy.u-strasbg.fr/nsmb/journal/v14/n2/full/nsmb1197.html doi:10.1038/nsmb1197]</ref> | ||
* At each end of the protein there is a barrel, which is constitued of a highly twisted ß-sheet and two helices called A and B at the <scene name='Sandbox_215/N-terminal/2'>N-terminal extremity</scene> and A', B' at C-terminal extremity. Helices B and B' are longer than helices A and A'. | * At each end of the protein there is a barrel, which is constitued of a highly twisted ß-sheet and two helices called A and B at the <scene name='Sandbox_215/N-terminal/2'>N-terminal extremity</scene> and A', B' at C-terminal extremity. Helices B and B' are longer than helices A and A'. | ||
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===Four lipid binding sites=== | ===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 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 lipids. Mutations affecting the neck block the transfer of neutral lipids. <ref | 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 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 lipids. Mutations affecting the neck block the transfer of neutral lipids. <ref name="Qui" /> | ||
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. | 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: a phosphatidylcholine, which buries its hydrophobic acyl chain inside the tunnel and its hydrophilic head groups to the solvent. | Each opening of the tunnel is plugged by one phospholipid: a phosphatidylcholine, which buries its hydrophobic acyl chain inside the tunnel and its hydrophilic head groups to the solvent. | ||
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===Mobile structures: Helix X and Ω flaps=== | ===Mobile structures: Helix X and Ω flaps=== | ||
Some mobile structures located near tunnel openings can facilitate the lipid transfer. | Some mobile structures located near tunnel openings can facilitate the lipid transfer. <ref name="Qui" /> | ||
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. | ||
