1fyh
From Proteopedia
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|PDB= 1fyh |SIZE=350|CAPTION= <scene name='initialview01'>1fyh</scene>, resolution 2.04Å | |PDB= 1fyh |SIZE=350|CAPTION= <scene name='initialview01'>1fyh</scene>, resolution 2.04Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CL:CHLORIDE ION'>CL</scene> | + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1d9c|1D9C]], [[1fg9|1FG9]], [[1eku|1EKU]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fyh OCA], [http://www.ebi.ac.uk/pdbsum/1fyh PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1fyh RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
BACKGROUND: Interferon-gamma (IFN-gamma) is a homodimeric cytokine that exerts its various activities by inducing the aggregation of two different receptors. The alpha chain receptor (IFN-gammaRalpha) is a high affinity receptor that binds to IFN-gamma in a symmetric bivalent manner to form a stable, intermediate 1:2 complex. This intermediate forms a binding template for the subsequent binding of two copies of the second receptor, beta chain receptor (IFN-gammaRbeta), producing the active 1:2:2 signaling complex. RESULTS: A single chain monovalent variant of IFN-gamma (scIFN-gamma) was constructed and complexed to one copy of the extracellular domain (ECD) of IFN-gammaRalpha. The structure of this 1:1 complex was determined and the hormone-receptor interface shown to be characterized by a number of hydrophilic interactions mediated by several highly ordered water networks. The scIFN-gamma interface consists of segments from each of the monomer chains of the homodimer. The principal hydrophobic contact of the receptor involves a tripeptide segment of the receptor having an unusual and high energy conformation. Despite containing only one binding site for IFN-gammaRalpha, the monovalent scIFN-gamma molecule has significant activity in antiviral biological assays. CONCLUSIONS: ScIFN-gamma binds the ECD of IFN-gammaRalpha through a highly hydrated interface with an important set of hormone-receptor contacts mediated through structured waters. Although the interface is highly hydrated, it supports tight binding and has a considerable degree of specificity. The biological activity of scIFN-gamma confirms that the scIFN-gamma:IFN-gammaRalpha complex represents a productive intermediate and that it can effectively recruit the other required component, IFN-gammaRbeta, to signal based on the 1:1:1 complex. | BACKGROUND: Interferon-gamma (IFN-gamma) is a homodimeric cytokine that exerts its various activities by inducing the aggregation of two different receptors. The alpha chain receptor (IFN-gammaRalpha) is a high affinity receptor that binds to IFN-gamma in a symmetric bivalent manner to form a stable, intermediate 1:2 complex. This intermediate forms a binding template for the subsequent binding of two copies of the second receptor, beta chain receptor (IFN-gammaRbeta), producing the active 1:2:2 signaling complex. RESULTS: A single chain monovalent variant of IFN-gamma (scIFN-gamma) was constructed and complexed to one copy of the extracellular domain (ECD) of IFN-gammaRalpha. The structure of this 1:1 complex was determined and the hormone-receptor interface shown to be characterized by a number of hydrophilic interactions mediated by several highly ordered water networks. The scIFN-gamma interface consists of segments from each of the monomer chains of the homodimer. The principal hydrophobic contact of the receptor involves a tripeptide segment of the receptor having an unusual and high energy conformation. Despite containing only one binding site for IFN-gammaRalpha, the monovalent scIFN-gamma molecule has significant activity in antiviral biological assays. CONCLUSIONS: ScIFN-gamma binds the ECD of IFN-gammaRalpha through a highly hydrated interface with an important set of hormone-receptor contacts mediated through structured waters. Although the interface is highly hydrated, it supports tight binding and has a considerable degree of specificity. The biological activity of scIFN-gamma confirms that the scIFN-gamma:IFN-gammaRalpha complex represents a productive intermediate and that it can effectively recruit the other required component, IFN-gammaRbeta, to signal based on the 1:1:1 complex. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: AIDS, rapid progression to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Aplastic anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], BCG infection, generalized familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107470 107470]], H. pylori infection, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107470 107470]], Hepatitis C virus, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Interferon, immune, deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Mycobacterial infection, atypical, familial disseminated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107470 107470]], TSC2 angiomyolipomas, renal, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Tuberculosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107470 107470]], Tuberculosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Kossiakoff, A A.]] | [[Category: Kossiakoff, A A.]] | ||
[[Category: Randal, M.]] | [[Category: Randal, M.]] | ||
| - | [[Category: CL]] | ||
[[Category: cytokine-receptor complex]] | [[Category: cytokine-receptor complex]] | ||
[[Category: fibronectin type-iii]] | [[Category: fibronectin type-iii]] | ||
| - | ''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 20:32:43 2008'' |
Revision as of 17:32, 30 March 2008
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| , resolution 2.04Å | |||||||
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| Ligands: | |||||||
| Related: | 1D9C, 1FG9, 1EKU
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
1:1 COMPLEX BETWEEN AN INTERFERON GAMMA SINGLE-CHAIN VARIANT AND ITS RECEPTOR
Overview
BACKGROUND: Interferon-gamma (IFN-gamma) is a homodimeric cytokine that exerts its various activities by inducing the aggregation of two different receptors. The alpha chain receptor (IFN-gammaRalpha) is a high affinity receptor that binds to IFN-gamma in a symmetric bivalent manner to form a stable, intermediate 1:2 complex. This intermediate forms a binding template for the subsequent binding of two copies of the second receptor, beta chain receptor (IFN-gammaRbeta), producing the active 1:2:2 signaling complex. RESULTS: A single chain monovalent variant of IFN-gamma (scIFN-gamma) was constructed and complexed to one copy of the extracellular domain (ECD) of IFN-gammaRalpha. The structure of this 1:1 complex was determined and the hormone-receptor interface shown to be characterized by a number of hydrophilic interactions mediated by several highly ordered water networks. The scIFN-gamma interface consists of segments from each of the monomer chains of the homodimer. The principal hydrophobic contact of the receptor involves a tripeptide segment of the receptor having an unusual and high energy conformation. Despite containing only one binding site for IFN-gammaRalpha, the monovalent scIFN-gamma molecule has significant activity in antiviral biological assays. CONCLUSIONS: ScIFN-gamma binds the ECD of IFN-gammaRalpha through a highly hydrated interface with an important set of hormone-receptor contacts mediated through structured waters. Although the interface is highly hydrated, it supports tight binding and has a considerable degree of specificity. The biological activity of scIFN-gamma confirms that the scIFN-gamma:IFN-gammaRalpha complex represents a productive intermediate and that it can effectively recruit the other required component, IFN-gammaRbeta, to signal based on the 1:1:1 complex.
About this Structure
1FYH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structure and activity of a monomeric interferon-gamma:alpha-chain receptor signaling complex., Randal M, Kossiakoff AA, Structure. 2001 Feb 7;9(2):155-63. PMID:11250200
Page seeded by OCA on Sun Mar 30 20:32:43 2008
