1ilk
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ilk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ilk OCA], [http://www.ebi.ac.uk/pdbsum/1ilk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ilk RCSB]</span> | ||
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==Overview== | ==Overview== | ||
BACKGROUND: Interleukin (IL)-10 is a cytokine that inhibits production of other regulatory factors, including interferon gamma (IFN-gamma) and IL-2. A dimer of IL-10 is present in solution and is presumed to participate in receptor binding, but the nature of the dimer has not been previously reported. An atomic model is necessary to interpret biological activity of IL-10 and to design mutants with agonistic or antagonistic properties. RESULTS: The X-ray crystal structure of a recombinant form of human IL-10 has been solved at 1.8 A resolution and refined to a crystallographic R-factor of 0.156. The molecule is a tight dimer made of two interpenetrating subunits, forming a V-shaped structure. Each half of the structure consists of a six alpha-helices, four originating from one subunit and two from the other. Four of the helices form a classical 'up-up-down-down' bundle observed in all other helical cytokines. The overall topology of the helices bears close resemblance to IFN gamma, although the similarity is less striking when examined in greater detail. CONCLUSIONS: The topological similarity of IL-10 to IFN gamma was totally unexpected, and may be a reflection of the close relationship between the biological effects of these two cytokines. The structure of IL-10 provides insights into the possible modes of conversion of the dimer into monomers, and of putative sites of receptor interactions. The good level of refinement and high resolution of this structure show that the internal disorder often associated with other helical cytokines is not an essential feature of this class of proteins. | BACKGROUND: Interleukin (IL)-10 is a cytokine that inhibits production of other regulatory factors, including interferon gamma (IFN-gamma) and IL-2. A dimer of IL-10 is present in solution and is presumed to participate in receptor binding, but the nature of the dimer has not been previously reported. An atomic model is necessary to interpret biological activity of IL-10 and to design mutants with agonistic or antagonistic properties. RESULTS: The X-ray crystal structure of a recombinant form of human IL-10 has been solved at 1.8 A resolution and refined to a crystallographic R-factor of 0.156. The molecule is a tight dimer made of two interpenetrating subunits, forming a V-shaped structure. Each half of the structure consists of a six alpha-helices, four originating from one subunit and two from the other. Four of the helices form a classical 'up-up-down-down' bundle observed in all other helical cytokines. The overall topology of the helices bears close resemblance to IFN gamma, although the similarity is less striking when examined in greater detail. CONCLUSIONS: The topological similarity of IL-10 to IFN gamma was totally unexpected, and may be a reflection of the close relationship between the biological effects of these two cytokines. The structure of IL-10 provides insights into the possible modes of conversion of the dimer into monomers, and of putative sites of receptor interactions. The good level of refinement and high resolution of this structure show that the internal disorder often associated with other helical cytokines is not an essential feature of this class of proteins. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Graft-versus-host disease, protection against OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124092 124092]], HIV-1, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124092 124092]], Rheumatoid arthritis, progression of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=124092 124092]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: cytokine]] | [[Category: cytokine]] | ||
| - | ''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 21:21:23 2008'' |
Revision as of 18:21, 30 March 2008
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| , resolution 1.8Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
INTERLEUKIN-10 CRYSTAL STRUCTURE REVEALS THE FUNCTIONAL DIMER WITH AN UNEXPECTED TOPOLOGICAL SIMILARITY TO INTERFERON GAMMA
Overview
BACKGROUND: Interleukin (IL)-10 is a cytokine that inhibits production of other regulatory factors, including interferon gamma (IFN-gamma) and IL-2. A dimer of IL-10 is present in solution and is presumed to participate in receptor binding, but the nature of the dimer has not been previously reported. An atomic model is necessary to interpret biological activity of IL-10 and to design mutants with agonistic or antagonistic properties. RESULTS: The X-ray crystal structure of a recombinant form of human IL-10 has been solved at 1.8 A resolution and refined to a crystallographic R-factor of 0.156. The molecule is a tight dimer made of two interpenetrating subunits, forming a V-shaped structure. Each half of the structure consists of a six alpha-helices, four originating from one subunit and two from the other. Four of the helices form a classical 'up-up-down-down' bundle observed in all other helical cytokines. The overall topology of the helices bears close resemblance to IFN gamma, although the similarity is less striking when examined in greater detail. CONCLUSIONS: The topological similarity of IL-10 to IFN gamma was totally unexpected, and may be a reflection of the close relationship between the biological effects of these two cytokines. The structure of IL-10 provides insights into the possible modes of conversion of the dimer into monomers, and of putative sites of receptor interactions. The good level of refinement and high resolution of this structure show that the internal disorder often associated with other helical cytokines is not an essential feature of this class of proteins.
About this Structure
1ILK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma., Zdanov A, Schalk-Hihi C, Gustchina A, Tsang M, Weatherbee J, Wlodawer A, Structure. 1995 Jun 15;3(6):591-601. PMID:8590020
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