1fg9
From Proteopedia
(New page: 200px<br /> <applet load="1fg9" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fg9, resolution 2.9Å" /> '''3:1 COMPLEX OF INTER...) |
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caption="1fg9, resolution 2.9Å" /> | caption="1fg9, resolution 2.9Å" /> | ||
'''3:1 COMPLEX OF INTERFERON-GAMMA RECEPTOR WITH INTERFERON-GAMMA DIMER'''<br /> | '''3:1 COMPLEX OF INTERFERON-GAMMA RECEPTOR WITH INTERFERON-GAMMA DIMER'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Molecular interactions among cytokines and cytokine receptors | + | BACKGROUND: Molecular interactions among cytokines and cytokine receptors form the basis of many cell-signaling pathways relevant to immune function. Interferon-gamma (IFN-gamma) signals through a multimeric receptor complex consisting of two different but structurally related transmembrane chains: the high-affinity receptor-binding subunit (IFN-gammaRalpha) and a species-specific accessory factor (AF-1 or IFN-gammaRbeta). In the signaling complex, the two receptors probably interact with one another through their extracellular domains. Understanding the atomic interactions of signaling complexes enhances the ability to control and alter cell signaling and also provides a greater understanding of basic biochemical processes. RESULTS: The crystal structure of the complex of human IFN-gamma with the soluble, glycosylated extracellular part of IFN-gammaRalpha has been determined at 2.9 A resolution using multiwavelength anomalous diffraction methods. In addition to the expected 2:1 complex, the crystal structure reveals the presence of a third receptor molecule not directly associated with the IFN-gamma dimer. Two distinct intermolecular contacts, involving the edge strands of the C-terminal domains, are observed between this extra receptor and the 2:1 receptor-ligand complex thereby forming a 3:1 complex. CONCLUSIONS: The observed interactions in the 2:1 complex of the high-affinity cell-surface receptor with the IFN-gamma cytokine are similar to those seen in a previously reported structure where the receptor chains were not glycosylated. The formation of beta-sheet packing interactions between pairs of IFN-gammaRalpha receptors in these crystals suggests a possible model for receptor oligomerization of Ralpha and the structurally homologous Rbeta receptors in the fully active IFN-gamma signaling complex. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FG9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1FG9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1FG9 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Arcy, A | + | [[Category: Arcy, A D.]] |
[[Category: Chene, C.]] | [[Category: Chene, C.]] | ||
| - | [[Category: Du, M | + | [[Category: Du, M H.le.]] |
| - | [[Category: Ealick, S | + | [[Category: Ealick, S E.]] |
[[Category: Fountoulakis, M.]] | [[Category: Fountoulakis, M.]] | ||
[[Category: Garotta, G.]] | [[Category: Garotta, G.]] | ||
| - | [[Category: Thiel, D | + | [[Category: Thiel, D J.]] |
| - | [[Category: Walter, R | + | [[Category: Walter, R L.]] |
| - | [[Category: Winkler, F | + | [[Category: Winkler, F K.]] |
[[Category: cytokine-receptor complex]] | [[Category: cytokine-receptor complex]] | ||
[[Category: fibronectin type-iii]] | [[Category: fibronectin type-iii]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:38:21 2008'' |
Revision as of 10:38, 21 February 2008
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3:1 COMPLEX OF INTERFERON-GAMMA RECEPTOR WITH INTERFERON-GAMMA DIMER
Contents |
Overview
BACKGROUND: Molecular interactions among cytokines and cytokine receptors form the basis of many cell-signaling pathways relevant to immune function. Interferon-gamma (IFN-gamma) signals through a multimeric receptor complex consisting of two different but structurally related transmembrane chains: the high-affinity receptor-binding subunit (IFN-gammaRalpha) and a species-specific accessory factor (AF-1 or IFN-gammaRbeta). In the signaling complex, the two receptors probably interact with one another through their extracellular domains. Understanding the atomic interactions of signaling complexes enhances the ability to control and alter cell signaling and also provides a greater understanding of basic biochemical processes. RESULTS: The crystal structure of the complex of human IFN-gamma with the soluble, glycosylated extracellular part of IFN-gammaRalpha has been determined at 2.9 A resolution using multiwavelength anomalous diffraction methods. In addition to the expected 2:1 complex, the crystal structure reveals the presence of a third receptor molecule not directly associated with the IFN-gamma dimer. Two distinct intermolecular contacts, involving the edge strands of the C-terminal domains, are observed between this extra receptor and the 2:1 receptor-ligand complex thereby forming a 3:1 complex. CONCLUSIONS: The observed interactions in the 2:1 complex of the high-affinity cell-surface receptor with the IFN-gamma cytokine are similar to those seen in a previously reported structure where the receptor chains were not glycosylated. The formation of beta-sheet packing interactions between pairs of IFN-gammaRalpha receptors in these crystals suggests a possible model for receptor oligomerization of Ralpha and the structurally homologous Rbeta receptors in the fully active IFN-gamma signaling complex.
Disease
Known diseases associated with this structure: AIDS, rapid progression to OMIM:[147570], Aplastic anemia OMIM:[147570], BCG infection, generalized familial OMIM:[107470], H. pylori infection, susceptibility to OMIM:[107470], Hepatitis C virus, resistance to OMIM:[147570], Interferon, immune, deficiency OMIM:[147570], Mycobacterial infection, atypical, familial disseminated OMIM:[107470], TSC2 angiomyolipomas, renal, modifier of OMIM:[147570], Tuberculosis, susceptibility to OMIM:[107470], Tuberculosis, susceptibility to OMIM:[147570]
About this Structure
1FG9 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex., Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chene C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE, Structure. 2000 Sep 15;8(9):927-36. PMID:10986460
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