1fg9

From Proteopedia

(Difference between revisions)

Current revision

3:1 COMPLEX OF INTERFERON-GAMMA RECEPTOR WITH INTERFERON-GAMMA DIMER

Structural highlights

1fg9 is a 5 chain structure with sequence from Homo sapiens. The August 2010 RCSB PDB Molecule of the Month feature on Interferons by David Goodsell is 10.2210/rcsb_pdb/mom_2010_8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
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: 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.

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^[1]

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

References

↑ Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chene C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE. Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure. 2000 Sep 15;8(9):927-36. PMID:10986460

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/1fg9"

@@ Line 1: / Line 1: @@
 ==3:1 COMPLEX OF INTERFERON-GAMMA RECEPTOR WITH INTERFERON-GAMMA DIMER==
-<StructureSection load='1fg9' size='340' side='right' caption='[[1fg9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='1fg9' size='340' side='right'caption='[[1fg9]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1fg9]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The August 2010 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Interferons''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2010_8 10.2210/rcsb_pdb/mom_2010_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FG9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1FG9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1fg9]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The August 2010 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Interferons''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2010_8 10.2210/rcsb_pdb/mom_2010_8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FG9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FG9 FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fg9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fg9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1fg9 RCSB], [http://www.ebi.ac.uk/pdbsum/1fg9 PDBsum]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</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=1fg9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fg9 OCA], [https://pdbe.org/1fg9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fg9 RCSB], [https://www.ebi.ac.uk/pdbsum/1fg9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fg9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/IFNG_HUMAN IFNG_HUMAN]] In Caucasians, genetic variation in IFNG is associated with the risk of aplastic anemia (AA) [MIM:[http://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. [[http://www.uniprot.org/uniprot/INGR1_HUMAN INGR1_HUMAN]] Defects in IFNGR1 are a cause of Mendelian susceptibility to mycobacterial disease (MSMD) [MIM:[http://omim.org/entry/209950 209950]]; also known as familial disseminated atypical mycobacterial infection. This rare condition confers predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine and environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals. The pathogenic mechanism underlying MSMD is the impairment of interferon-gamma mediated immunity whose severity determines the clinical outcome. Some patients die of overwhelming mycobacterial disease with lepromatous-like lesions in early childhood, whereas others develop, later in life, disseminated but curable infections with tuberculoid granulomas. MSMD is a genetically heterogeneous disease with autosomal recessive, autosomal dominant or X-linked inheritance.<ref>PMID:9389728</ref> <ref>PMID:10811850</ref>
+[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 ==
-[[http://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. [[http://www.uniprot.org/uniprot/INGR1_HUMAN INGR1_HUMAN]] Receptor for interferon gamma. Two receptors bind one interferon gamma dimer.
+[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/fg/1fg9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fg/1fg9_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=1fg9 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 29: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1fg9" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Interferon|Interferon]]
+*[[Interferon 3D structures|Interferon 3D structures]]
-*[[Interferon receptor|Interferon receptor]]
+*[[Interferon receptor 3D structures|Interferon receptor 3D structures]]
 == References ==
 <references/>
@@ Line 37: / Line 40: @@
 [[Category: Homo sapiens]]
 [[Category: Interferons]]
+[[Category: Large Structures]]
 [[Category: RCSB PDB Molecule of the Month]]
-[[Category: Arcy, A D]]
+[[Category: Chene C]]
-[[Category: Chene, C]]
+[[Category: D'Arcy A]]
-[[Category: Du, M H.le]]
+[[Category: Ealick SE]]
-[[Category: Ealick, S E]]
+[[Category: Fountoulakis M]]
-[[Category: Fountoulakis, M]]
+[[Category: Garotta G]]
-[[Category: Garotta, G]]
+[[Category: Thiel DJ]]
-[[Category: Thiel, D J]]
+[[Category: Walter RL]]
-[[Category: Walter, R L]]
+[[Category: Winkler FK]]
-[[Category: Winkler, F K]]
+[[Category: Le Du M-H]]
-[[Category: Cytokine-receptor complex]]
-[[Category: Fibronectin type-iii]]
-[[Category: Immune system]]

1fg9

From Proteopedia

Current revision

3:1 COMPLEX OF INTERFERON-GAMMA RECEPTOR WITH INTERFERON-GAMMA DIMER

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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