1tnf
From Proteopedia
(New page: 200px<br /> <applet load="1tnf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tnf, resolution 2.6Å" /> '''THE STRUCTURE OF TUM...) |
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| - | [[Image:1tnf.gif|left|200px]]<br /> | + | [[Image:1tnf.gif|left|200px]]<br /><applet load="1tnf" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1tnf, resolution 2.6Å" /> | caption="1tnf, resolution 2.6Å" /> | ||
'''THE STRUCTURE OF TUMOR NECROSIS FACTOR-ALPHA AT 2.6 ANGSTROMS RESOLUTION. IMPLICATIONS FOR RECEPTOR BINDING'''<br /> | '''THE STRUCTURE OF TUMOR NECROSIS FACTOR-ALPHA AT 2.6 ANGSTROMS RESOLUTION. IMPLICATIONS FOR RECEPTOR BINDING'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The three-dimensional structure of tumor necrosis factor (TNF-alpha), a | + | The three-dimensional structure of tumor necrosis factor (TNF-alpha), a protein hormone secreted by macrophages, has been determined at 2.6 A resolution by x-ray crystallography. Phases were determined by multiple isomorphous replacement using data collected from five heavy atom derivatives. The multiple isomorphous replacement phases were further improved by real space symmetry averaging, exploiting the noncrystallographic 3-fold symmetry of the TNF-alpha trimer. An atomic model corresponding to the known amino acid sequence of TNF-alpha was readily built into the electron density map calculated with these improved phases. The 17,350-dalton monomer forms an elongated, antiparallel beta-pleated sheet sandwich with a "jelly-roll" topology. Three monomers associate intimately about a 3-fold axis of symmetry to form a compact bell-shaped trimer. Examination of the model and comparison to known protein structures reveals striking structural homology to several viral coat proteins, particularly satellite tobacco necrosis virus. Locations of residues conserved between TNF-alpha and lymphotoxin (TNF-beta, a related cytokine known to bind to the same receptors as TNF-alpha) suggest that lymphotoxin, like TNF-alpha, binds to the receptor as a trimer and that the general site of interaction with the receptor is at the "base" of the trimer. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TNF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1TNF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TNF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Eck, M | + | [[Category: Eck, M J.]] |
| - | [[Category: Sprang, S | + | [[Category: Sprang, S R.]] |
[[Category: lymphokine]] | [[Category: lymphokine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:15:22 2008'' |
Revision as of 13:15, 21 February 2008
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THE STRUCTURE OF TUMOR NECROSIS FACTOR-ALPHA AT 2.6 ANGSTROMS RESOLUTION. IMPLICATIONS FOR RECEPTOR BINDING
Contents |
Overview
The three-dimensional structure of tumor necrosis factor (TNF-alpha), a protein hormone secreted by macrophages, has been determined at 2.6 A resolution by x-ray crystallography. Phases were determined by multiple isomorphous replacement using data collected from five heavy atom derivatives. The multiple isomorphous replacement phases were further improved by real space symmetry averaging, exploiting the noncrystallographic 3-fold symmetry of the TNF-alpha trimer. An atomic model corresponding to the known amino acid sequence of TNF-alpha was readily built into the electron density map calculated with these improved phases. The 17,350-dalton monomer forms an elongated, antiparallel beta-pleated sheet sandwich with a "jelly-roll" topology. Three monomers associate intimately about a 3-fold axis of symmetry to form a compact bell-shaped trimer. Examination of the model and comparison to known protein structures reveals striking structural homology to several viral coat proteins, particularly satellite tobacco necrosis virus. Locations of residues conserved between TNF-alpha and lymphotoxin (TNF-beta, a related cytokine known to bind to the same receptors as TNF-alpha) suggest that lymphotoxin, like TNF-alpha, binds to the receptor as a trimer and that the general site of interaction with the receptor is at the "base" of the trimer.
Disease
Known diseases associated with this structure: Asthma, susceptibility to OMIM:[191160], Dementia, vascular, susceptibility to OMIM:[191160], Malaria, cerebral, susceptibility to OMIM:[191160], Migraine without aura, susceptibility to OMIM:[191160], Septic shock, susceptibility to OMIM:[191160]
About this Structure
1TNF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding., Eck MJ, Sprang SR, J Biol Chem. 1989 Oct 15;264(29):17595-605. PMID:2551905
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