1dg6
From Proteopedia
(New page: 200px<br /> <applet load="1dg6" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dg6, resolution 1.30Å" /> '''CRYSTAL STRUCTURE O...) |
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| - | [[Image:1dg6.gif|left|200px]]<br /> | + | [[Image:1dg6.gif|left|200px]]<br /><applet load="1dg6" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1dg6" size=" | + | |
caption="1dg6, resolution 1.30Å" /> | caption="1dg6, resolution 1.30Å" /> | ||
'''CRYSTAL STRUCTURE OF APO2L/TRAIL'''<br /> | '''CRYSTAL STRUCTURE OF APO2L/TRAIL'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Apoptosis-inducing ligand 2 (Apo2L, also called TRAIL), a member of the | + | Apoptosis-inducing ligand 2 (Apo2L, also called TRAIL), a member of the tumor necrosis factor (TNF) family, induces apoptosis in a variety of human tumor cell lines but not in normal cells [Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C.-P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., Smith, C. A., and Goodwin, R. G. (1995) Immunity 3, 673-682; Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A., and Ashkenazi, A. (1996) J. Biol. Chem. 271, 12687-12690]. Here we describe the structure of Apo2L at 1.3 A resolution and use alanine-scanning mutagenesis to map the receptor contact regions. The structure reveals a homotrimeric protein that resembles TNF with receptor-binding epitopes at the interface between monomers. A zinc ion is buried at the trimer interface, coordinated by the single cysteine residue of each monomer. The zinc ion is required for maintaining the native structure and stability and, hence, the biological activity of Apo2L. This is the first example of metal-dependent oligomerization and function of a cytokine. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DG6 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 ZN and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1DG6 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=ZN:'>ZN</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DG6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: ConnelL, M | + | [[Category: ConnelL, M P.O.]] |
| - | [[Category: Hymowitz, S | + | [[Category: Hymowitz, S G.]] |
| - | [[Category: Kelley, R | + | [[Category: Kelley, R F.]] |
| - | [[Category: Ultsch, M | + | [[Category: Ultsch, M H.]] |
| - | [[Category: Vos, A | + | [[Category: Vos, A M.de.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: ZN]] | [[Category: ZN]] | ||
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[[Category: zinc-binding site]] | [[Category: zinc-binding site]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:16:20 2008'' |
Revision as of 10:16, 21 February 2008
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CRYSTAL STRUCTURE OF APO2L/TRAIL
Contents |
Overview
Apoptosis-inducing ligand 2 (Apo2L, also called TRAIL), a member of the tumor necrosis factor (TNF) family, induces apoptosis in a variety of human tumor cell lines but not in normal cells [Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C.-P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., Smith, C. A., and Goodwin, R. G. (1995) Immunity 3, 673-682; Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A., and Ashkenazi, A. (1996) J. Biol. Chem. 271, 12687-12690]. Here we describe the structure of Apo2L at 1.3 A resolution and use alanine-scanning mutagenesis to map the receptor contact regions. The structure reveals a homotrimeric protein that resembles TNF with receptor-binding epitopes at the interface between monomers. A zinc ion is buried at the trimer interface, coordinated by the single cysteine residue of each monomer. The zinc ion is required for maintaining the native structure and stability and, hence, the biological activity of Apo2L. This is the first example of metal-dependent oligomerization and function of a cytokine.
Disease
Known disease associated with this structure: Squamous cell carcinoma, head and neck OMIM:[603612]
About this Structure
1DG6 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
A unique zinc-binding site revealed by a high-resolution X-ray structure of homotrimeric Apo2L/TRAIL., Hymowitz SG, O'Connell MP, Ultsch MH, Hurst A, Totpal K, Ashkenazi A, de Vos AM, Kelley RF, Biochemistry. 2000 Feb 1;39(4):633-40. PMID:10651627
Page seeded by OCA on Thu Feb 21 12:16:20 2008
Categories: Homo sapiens | Single protein | ConnelL, M P.O. | Hymowitz, S G. | Kelley, R F. | Ultsch, M H. | Vos, A M.de. | CL | ZN | Cytokine | Tnf | Trimer | Zinc-binding site
