1dg6
From Proteopedia
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|PDB= 1dg6 |SIZE=350|CAPTION= <scene name='initialview01'>1dg6</scene>, resolution 1.30Å | |PDB= 1dg6 |SIZE=350|CAPTION= <scene name='initialview01'>1dg6</scene>, resolution 1.30Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dg6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dg6 OCA], [http://www.ebi.ac.uk/pdbsum/1dg6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dg6 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known disease associated with this structure: Squamous cell carcinoma, head and neck OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603612 603612]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Ultsch, M H.]] | [[Category: Ultsch, M H.]] | ||
[[Category: Vos, A M.de.]] | [[Category: Vos, A M.de.]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: ZN]] | ||
[[Category: cytokine]] | [[Category: cytokine]] | ||
[[Category: tnf]] | [[Category: tnf]] | ||
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[[Category: zinc-binding site]] | [[Category: zinc-binding site]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:41:02 2008'' |
Revision as of 16:41, 30 March 2008
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| , resolution 1.30Å | |||||||
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| Ligands: | , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF APO2L/TRAIL
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.
About this Structure
1DG6 is a Single protein structure of sequence from Homo sapiens. 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 Sun Mar 30 19:41:02 2008
