Sandbox 215: Difference between revisions
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<Structure load='2obd' size='400' frame='true' align='left' caption='Structure of cholesteryl ester transfer protein' scene='Insert optional scene name here' (PDB entry [[2obd]])'/>2OBD is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo Sapiens]. Full crystallographic information is available from [http://www.ebi.ac.uk/msd-srv/oca/oca-bin/ocashort?id=2OBD OCA] | <Structure load='2obd' size='400' frame='true' align='left' caption='Structure of cholesteryl ester transfer protein' scene='Insert optional scene name here' (PDB entry [[2obd]])'/>2OBD is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo Sapiens]. Full crystallographic information is available from [http://www.ebi.ac.uk/msd-srv/oca/oca-bin/ocashort?id=2OBD OCA] | ||
=== | ===Overview of the structure=== | ||
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>. | ||
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* At the <scene name='Sandbox_215/C-terminal/1'>C-terminal</scene> extremity there is a distorted amphiphathic helix called <scene name='Sandbox_215/Helix_x/1'>helix X</scene> which is an extension of C-teminal extremity interacting with N-terminal residues. | * At the <scene name='Sandbox_215/C-terminal/1'>C-terminal</scene> extremity there is a distorted amphiphathic helix called <scene name='Sandbox_215/Helix_x/1'>helix X</scene> which is an extension of C-teminal extremity interacting with N-terminal residues. | ||
=== | ===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>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'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>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> | ||
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*Cholesteryl ester 2 (CE2) is situated between the central β-sheet and the C-barrel. CE2 penetrates deeper into the barrel than CE1. 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. | *Cholesteryl ester 2 (CE2) is situated between the central β-sheet and the C-barrel. CE2 penetrates deeper into the barrel than CE1. 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. | ||
=== | ===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. | ||