1fyh

From Proteopedia

(Difference between revisions)

Current revision

1:1 COMPLEX BETWEEN AN INTERFERON GAMMA SINGLE-CHAIN VARIANT AND ITS RECEPTOR

Structural highlights

1fyh is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.04Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IFNG_HUMAN In Caucasians, genetic variation in IFNG is associated with the risk of aplastic anemia (AA) [MIM:609135. AA is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. In most patients, the stem cell lesion is caused by an autoimmune attack. T-lymphocytes, activated by an endogenous or exogenous, and most often unknown antigenic stimulus, secrete cytokines, including IFN-gamma, which would in turn be able to suppress hematopoiesis.

Function

IFNG_HUMAN Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Randal M, Kossiakoff AA. The structure and activity of a monomeric interferon-gamma:alpha-chain receptor signaling complex. Structure. 2001 Feb 7;9(2):155-63. PMID:11250200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1fyh"

Categories: Homo sapiens | Large Structures | Kossiakoff AA | Randal M

@@ Line 1: / Line 1: @@
-[[Image:1fyh.jpg|left|200px]]<br /><applet load="1fyh" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1fyh, resolution 2.04&Aring;" />
-'''1:1 COMPLEX BETWEEN AN INTERFERON GAMMA SINGLE-CHAIN VARIANT AND ITS RECEPTOR'''<br />
-==Overview==
+==1:1 COMPLEX BETWEEN AN INTERFERON GAMMA SINGLE-CHAIN VARIANT AND ITS RECEPTOR==
-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.
+<StructureSection load='1fyh' size='340' side='right'caption='[[1fyh]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1fyh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FYH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.04&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1fyh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fyh OCA], [https://pdbe.org/1fyh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fyh RCSB], [https://www.ebi.ac.uk/pdbsum/1fyh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fyh ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/IFNG_HUMAN IFNG_HUMAN] In Caucasians, genetic variation in IFNG is associated with the risk of aplastic anemia (AA) [MIM:[https://omim.org/entry/609135 609135]. AA is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. In most patients, the stem cell lesion is caused by an autoimmune attack. T-lymphocytes, activated by an endogenous or exogenous, and most often unknown antigenic stimulus, secrete cytokines, including IFN-gamma, which would in turn be able to suppress hematopoiesis.
+== Function ==
+[https://www.uniprot.org/uniprot/IFNG_HUMAN IFNG_HUMAN] Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fy/1fyh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1fyh ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-==Disease==
+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<ref>PMID:11250200</ref>
-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==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-FYH is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FYH OCA].
+</div>
+<div class="pdbe-citations 1fyh" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11250200 11250200]
+*[[Interferon 3D structures|Interferon 3D structures]]
+*[[Interferon receptor 3D structures|Interferon receptor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Kossiakoff, A.A.]]
+[[Category: Kossiakoff AA]]
-[[Category: Randal, M.]]
+[[Category: Randal M]]
-[[Category: CL]]
-[[Category: cytokine-receptor complex]]
-[[Category: fibronectin type-iii]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:49:52 2008''

1fyh

From Proteopedia

Current revision

1:1 COMPLEX BETWEEN AN INTERFERON GAMMA SINGLE-CHAIN VARIANT AND ITS RECEPTOR

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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