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| - | {{STRUCTURE_1ilt| PDB=1ilt | SCENE= }}
| + | ==X-RAY STRUCTURE OF INTERLEUKIN-1 RECEPTOR ANTAGONIST AT 2.0 ANGSTROMS RESOLUTION== |
| - | ===X-RAY STRUCTURE OF INTERLEUKIN-1 RECEPTOR ANTAGONIST AT 2.0 ANGSTROMS RESOLUTION===
| + | <StructureSection load='1ilt' size='340' side='right' caption='[[1ilt]], [[Resolution|resolution]] 2.00Å' scene=''> |
| - | {{ABSTRACT_PUBMED_8175703}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1ilt]] is a 2 chain structure with sequence 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=1ILT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ILT FirstGlance]. <br> |
| | + | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ilt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ilt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ilt RCSB], [http://www.ebi.ac.uk/pdbsum/1ilt PDBsum]</span></td></tr> |
| | + | <table> |
| | + | == Disease == |
| | + | [[http://www.uniprot.org/uniprot/IL1RA_HUMAN IL1RA_HUMAN]] Genetic variation in IL1RN is associated with susceptibility to microvascular complications of diabetes type 4 (MVCD4) [MIM:[http://omim.org/entry/612628 612628]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Defects in IL1RN are the cause of interleukin 1 receptor antagonist deficiency (DIRA) [MIM:[http://omim.org/entry/612852 612852]]; also known as deficiency of interleukin 1 receptor antagonist. Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T-cells. DIRA is a rare, autosomal recessive, genetic autoinflammatory disease that results in sterile multifocal osteomyelitis (bone inflammation in multiple places), periostitis (inflammation of the membrane surrounding the bones), and pustulosis (due to skin inflammation) from birth.<ref>PMID:19494218</ref> |
| | + | == Function == |
| | + | [[http://www.uniprot.org/uniprot/IL1RA_HUMAN IL1RA_HUMAN]] Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure.<ref>PMID:7775431</ref> |
| | + | == 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/il/1ilt_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Interleukin-1 receptor antagonist (IL-1ra) is a natural competitive antagonist of IL-1. In order to further elucidate the mechanism by which IL-1ra binds without activating the IL-1 receptor, we have solved the crystal structure of IL-1ra at 2.0-A resolution. IL-1ra has the same overall beta-trefoil fold as IL-1 alpha and IL-1 beta and has a very similar hydrophobic core. However, there are a number of structural differences between the molecules, including significant differences at the open end of the beta-barrel, which has been identified in IL-1 beta as a receptor binding site. |
| | | | |
| - | ==Disease==
| + | X-ray structure of interleukin-1 receptor antagonist at 2.0-A resolution.,Vigers GP, Caffes P, Evans RJ, Thompson RC, Eisenberg SP, Brandhuber BJ J Biol Chem. 1994 Apr 29;269(17):12874-9. PMID:8175703<ref>PMID:8175703</ref> |
| - | [[http://www.uniprot.org/uniprot/IL1RA_HUMAN IL1RA_HUMAN]] Genetic variation in IL1RN is associated with susceptibility to microvascular complications of diabetes type 4 (MVCD4) [MIM:[http://omim.org/entry/612628 612628]]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Defects in IL1RN are the cause of interleukin 1 receptor antagonist deficiency (DIRA) [MIM:[http://omim.org/entry/612852 612852]]; also known as deficiency of interleukin 1 receptor antagonist. Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T-cells. DIRA is a rare, autosomal recessive, genetic autoinflammatory disease that results in sterile multifocal osteomyelitis (bone inflammation in multiple places), periostitis (inflammation of the membrane surrounding the bones), and pustulosis (due to skin inflammation) from birth.<ref>PMID:19494218</ref>
| + | |
| | | | |
| - | ==Function==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[http://www.uniprot.org/uniprot/IL1RA_HUMAN IL1RA_HUMAN]] Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure.<ref>PMID:7775431</ref>
| + | </div> |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | [[1ilt]] is a 2 chain structure with sequence 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=1ILT OCA].
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Interleukin-1 receptor antagonist|Interleukin-1 receptor antagonist]] | | *[[Interleukin-1 receptor antagonist|Interleukin-1 receptor antagonist]] |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:008175703</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Brandhuber, B J.]] | | [[Category: Brandhuber, B J.]] |
| | [[Category: Vigers, G P.A.]] | | [[Category: Vigers, G P.A.]] |
| | [[Category: Cytokine]] | | [[Category: Cytokine]] |
| Structural highlights
1ilt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Resources: | FirstGlance, OCA, RCSB, PDBsum |
Disease
[IL1RA_HUMAN] Genetic variation in IL1RN is associated with susceptibility to microvascular complications of diabetes type 4 (MVCD4) [MIM:612628]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Defects in IL1RN are the cause of interleukin 1 receptor antagonist deficiency (DIRA) [MIM:612852]; also known as deficiency of interleukin 1 receptor antagonist. Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T-cells. DIRA is a rare, autosomal recessive, genetic autoinflammatory disease that results in sterile multifocal osteomyelitis (bone inflammation in multiple places), periostitis (inflammation of the membrane surrounding the bones), and pustulosis (due to skin inflammation) from birth.[1]
Function
[IL1RA_HUMAN] Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure.[2]
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
Interleukin-1 receptor antagonist (IL-1ra) is a natural competitive antagonist of IL-1. In order to further elucidate the mechanism by which IL-1ra binds without activating the IL-1 receptor, we have solved the crystal structure of IL-1ra at 2.0-A resolution. IL-1ra has the same overall beta-trefoil fold as IL-1 alpha and IL-1 beta and has a very similar hydrophobic core. However, there are a number of structural differences between the molecules, including significant differences at the open end of the beta-barrel, which has been identified in IL-1 beta as a receptor binding site.
X-ray structure of interleukin-1 receptor antagonist at 2.0-A resolution.,Vigers GP, Caffes P, Evans RJ, Thompson RC, Eisenberg SP, Brandhuber BJ J Biol Chem. 1994 Apr 29;269(17):12874-9. PMID:8175703[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, Laxer R, Tedgard U, Cowen EW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone DL, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Lee CC, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009 Jun 4;360(23):2426-37. doi: 10.1056/NEJMoa0807865. PMID:19494218 doi:10.1056/NEJMoa0807865
- ↑ Greenfeder SA, Nunes P, Kwee L, Labow M, Chizzonite RA, Ju G. Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J Biol Chem. 1995 Jun 9;270(23):13757-65. PMID:7775431
- ↑ Vigers GP, Caffes P, Evans RJ, Thompson RC, Eisenberg SP, Brandhuber BJ. X-ray structure of interleukin-1 receptor antagonist at 2.0-A resolution. J Biol Chem. 1994 Apr 29;269(17):12874-9. PMID:8175703
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