1tjj
From Proteopedia
(New page: 200px<br /> <applet load="1tjj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tjj, resolution 2.00Å" /> '''Human GM2 Activator...) |
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| - | [[Image:1tjj.gif|left|200px]]<br /> | + | [[Image:1tjj.gif|left|200px]]<br /><applet load="1tjj" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1tjj" size=" | + | |
caption="1tjj, resolution 2.00Å" /> | caption="1tjj, resolution 2.00Å" /> | ||
'''Human GM2 Activator Protein PAF complex'''<br /> | '''Human GM2 Activator Protein PAF complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | GM2-activator protein (GM2-AP) is a lipid transfer protein that has the | + | GM2-activator protein (GM2-AP) is a lipid transfer protein that has the ability to stimulate the enzymatic processing of gangliosides as well as T-cell activation through lipid presentation. Our previous X-ray crystallographic studies of GM2-AP have revealed a large lipid binding pocket as the central overall feature of the structure with non-protein electron density within this pocket suggesting bound lipid. To extend these studies, we present here the 2A crystal structure of GM2-AP complexed with platelet activating factor (PAF). PAF is a potent phosphoacylglycerol whose toxic patho-physiological effects can be inhibited by GM2-AP. The structure shows an ordered arrangement of two bound lipids and a fatty acid molecule. One PAF molecule binds in an extended conformation within the hydrophobic channel that has an open and closed conformation, and was seen to contain bound phospholipid in the low pH apo structure. The second molecule is submerged inside the pocket in a U-shaped conformation with its head group near the single polar residue S141. It was refined as lyso-PAF as it lacks electron density for the sn-2 acetate group. The alkyl chains of PAF interact through van der Waals' contacts, while the head groups bind in different environments with their phosphocholine moieties in contact with aromatic rings (Y137, F80). The structure has revealed further insights into the lipid binding properties of GM2-AP, suggesting an unexpected unique mode of lipid packaging that may explain the efficiency of GM2-AP in inhibiting the detrimental biological effects of PAF. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TJJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ACT, CL, EPE, PFS, LPE, DAO and IPA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1TJJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=EPE:'>EPE</scene>, <scene name='pdbligand=PFS:'>PFS</scene>, <scene name='pdbligand=LPE:'>LPE</scene>, <scene name='pdbligand=DAO:'>DAO</scene> and <scene name='pdbligand=IPA:'>IPA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TJJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Mi, L | + | [[Category: Mi, L Z.]] |
[[Category: Rastinejad, F.]] | [[Category: Rastinejad, F.]] | ||
| - | [[Category: Wright, C | + | [[Category: Wright, C S.]] |
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: protein dynamics]] | [[Category: protein dynamics]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:14:12 2008'' |
Revision as of 13:14, 21 February 2008
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Human GM2 Activator Protein PAF complex
Contents |
Overview
GM2-activator protein (GM2-AP) is a lipid transfer protein that has the ability to stimulate the enzymatic processing of gangliosides as well as T-cell activation through lipid presentation. Our previous X-ray crystallographic studies of GM2-AP have revealed a large lipid binding pocket as the central overall feature of the structure with non-protein electron density within this pocket suggesting bound lipid. To extend these studies, we present here the 2A crystal structure of GM2-AP complexed with platelet activating factor (PAF). PAF is a potent phosphoacylglycerol whose toxic patho-physiological effects can be inhibited by GM2-AP. The structure shows an ordered arrangement of two bound lipids and a fatty acid molecule. One PAF molecule binds in an extended conformation within the hydrophobic channel that has an open and closed conformation, and was seen to contain bound phospholipid in the low pH apo structure. The second molecule is submerged inside the pocket in a U-shaped conformation with its head group near the single polar residue S141. It was refined as lyso-PAF as it lacks electron density for the sn-2 acetate group. The alkyl chains of PAF interact through van der Waals' contacts, while the head groups bind in different environments with their phosphocholine moieties in contact with aromatic rings (Y137, F80). The structure has revealed further insights into the lipid binding properties of GM2-AP, suggesting an unexpected unique mode of lipid packaging that may explain the efficiency of GM2-AP in inhibiting the detrimental biological effects of PAF.
Disease
Known disease associated with this structure: GM2-gangliosidosis, AB variant OMIM:[272750]
About this Structure
1TJJ is a Single protein structure of sequence from Homo sapiens with , , , , , and as ligands. Full crystallographic information is available from OCA.
Reference
Evidence for lipid packaging in the crystal structure of the GM2-activator complex with platelet activating factor., Wright CS, Mi LZ, Rastinejad F, J Mol Biol. 2004 Sep 10;342(2):585-92. PMID:15327957
Page seeded by OCA on Thu Feb 21 15:14:12 2008
Categories: Homo sapiens | Single protein | Mi, L Z. | Rastinejad, F. | Wright, C S. | ACT | CL | DAO | EPE | IPA | LPE | PFS | Beta-cup topology | Lipid binding pocket | Platelet activating factor | Protein dynamics
