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| - | [[Image:2irt.jpg|left|200px]] | |
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| - | {{Structure
| + | ==INITIAL CRYSTALLOGRAPHIC ANALYSES OF A RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN== |
| - | |PDB= 2irt |SIZE=350|CAPTION= <scene name='initialview01'>2irt</scene>, resolution 3.2Å
| + | <StructureSection load='2irt' size='340' side='right'caption='[[2irt]], [[Resolution|resolution]] 3.20Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[2irt]] is a 2 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=2IRT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IRT FirstGlance]. <br> |
| - | |ACTIVITY= | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | |GENE= | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2irt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2irt OCA], [https://pdbe.org/2irt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2irt RCSB], [https://www.ebi.ac.uk/pdbsum/2irt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2irt ProSAT]</span></td></tr> |
| - | }}
| + | </table> |
| | + | == Disease == |
| | + | [https://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:[https://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:[https://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 == |
| | + | [https://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/ir/2irt_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/main_output.php?pdb_ID=2irt ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''INITIAL CRYSTALLOGRAPHIC ANALYSES OF A RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST PROTEIN'''
| + | ==See Also== |
| - | | + | *[[Interleukin receptor antagonist|Interleukin receptor antagonist]] |
| - | | + | == References == |
| - | ==Overview== | + | <references/> |
| - | We report the crystallization of samples of a recombinant preparation of human interleukin-1 receptor antagonist protein (IRAP) and solution of the crystal structure by isomorphous replacement methods. Crystals were obtained by the hanging-drop vapor-diffusion method at 277 K from solutions of PEG 4000 containing sodium chloride, dithiothreitol and PIPES [sodium piperazione-N,N'-bis(2-ethanesulfonate)] buffer at pH 7.0. Crystals appear within about a week and grow as truncated tetragonal bipyramids to 0.3-0.6 mm on an edge. X-ray diffraction data from these crystals specify space group P4(3)2(1)2 and unit-cell dimensions of a = b = 72.35(26), c = 114.7(8) A and Z = 16 (two molecules per asymmetric unit). Fresh crystals diffract to about 2.3 A resolution. The search for heavy-atom derivatives has produced two, potassium gold cyanide and trimethyl lead chloride, as same-site, single-site derivatives. Inspection of an electron-density map at 4 A resolution calculated with these derivatives confirms that the IRAP molecule is a member of the interleukin-1 structural family.
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Disease==
| + | |
| - | Known diseases associated with this structure: Gastric cancer risk after H. pylori infection OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147679 147679]], Mental retardation, X-linked, 21/34 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300206 300206]]
| + | |
| - | | + | |
| - | ==About this Structure== | + | |
| - | 2IRT is a [[Single protein]] structure of 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=2IRT OCA].
| + | |
| - | | + | |
| - | ==Reference==
| + | |
| - | Initial crystallographic analysis of a recombinant human interleukin-1 receptor antagonist protein., Clancy LL, Finzel BC, Yem AW, Deibel MR Jr, Strakalaitis NA, Brunner DP, Sweet RM, Einspahr HM, Acta Crystallogr D Biol Crystallogr. 1994 Mar 1;50(Pt 2):197-201. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15299459 15299459]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Clancy, L L.]] | + | [[Category: Clancy LL]] |
| - | [[Category: Einspahr, H M.]] | + | [[Category: Einspahr HM]] |
| - | [[Category: Finzel, B C.]] | + | [[Category: Finzel BC]] |
| - | [[Category: signal protein]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:32:41 2008''
| + | |
| Structural highlights
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.
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
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