1rj7: Difference between revisions

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-[[Image:1rj7.gif|left|200px]]
- {{Structure
+==Crystal structure of EDA-A1==
-|PDB= 1rj7 |SIZE=350|CAPTION= <scene name='initialview01'>1rj7</scene>, resolution 2.30&Aring;
+<StructureSection load='1rj7' size='340' side='right'caption='[[1rj7]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND=
+<table><tr><td colspan='2'>[[1rj7]] is a 12 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=1RJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RJ7 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]] 2.3&#8491;</td></tr>
-|GENE= ED1, EDA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1rj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rj7 OCA], [https://pdbe.org/1rj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rj7 RCSB], [https://www.ebi.ac.uk/pdbsum/1rj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rj7 ProSAT]</span></td></tr>
-}}
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/EDA_HUMAN EDA_HUMAN] Defects in EDA are the cause of ectodermal dysplasia 1, hypohidrotic, X-linked (XHED) [MIM:[https://omim.org/entry/305100 305100]; also known as Christ-Siemens-Touraine syndrome or X-linked hypohidrotic ectodermal dysplasia (XLHED). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. XHED is a disease characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. XHED is the most common form of over 150 clinically distinct ectodermal dysplasias.<ref>PMID:8696334</ref> <ref>PMID:9683615</ref> <ref>PMID:9736768</ref> <ref>PMID:11309369</ref> <ref>PMID:11416205</ref> <ref>PMID:9630076</ref> <ref>PMID:9507389</ref> <ref>PMID:10469321</ref> <ref>PMID:10951256</ref> <ref>PMID:11343303</ref> <ref>PMID:11378824</ref> <ref>PMID:11295832</ref> <ref>PMID:11279189</ref> <ref>PMID:12225002</ref> <ref>PMID:12932274</ref> <ref>PMID:17256800</ref> <ref>PMID:18231121</ref> <ref>PMID:19438931</ref> <ref>PMID:19127222</ref> <ref>PMID:20486090</ref> <ref>PMID:20979233</ref> <ref>PMID:22008666</ref> <ref>PMID:22350046</ref>   Defects in EDA are the cause of tooth agenesis selective X-linked type 1 (STHAGX1) [MIM:[https://omim.org/entry/313500 313500]. A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth).<ref>PMID:16583127</ref> <ref>PMID:18657636</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/EDA_HUMAN EDA_HUMAN] Seems to be involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Isoform 1 binds only to the receptor EDAR, while isoform 3 binds exclusively to the receptor XEDAR.
+== 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/rj/1rj7_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=1rj7 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+EDA is a tumor necrosis factor family member involved in ectodermal development. Splice variants EDA-A1 and EDA-A2 differ only by the presence of Glu 308 and Val 309 in the expected receptor binding region of EDA-A1 but not EDA-A2. This two amino acid difference functions as a switch controlling receptor specificity. EDA-A1 binds only to EDAR, while EDA-A2 is specific for XEDAR. In order to understand the structural basis of this switch, we determined the X-ray crystal structures of the TNF domain of both EDA-A1 and EDA-A2 at 2.3 A and 2.2 A, respectively. While the backbone conformation around the splice difference is similar in both isoforms, the conformation of the following loop, the surface charge, and the shape of the expected receptor binding site differ significantly.
-'''Crystal structure of EDA-A1'''
+The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct receptor specificity.,Hymowitz SG, Compaan DM, Yan M, Wallweber HJ, Dixit VM, Starovasnik MA, de Vos AM Structure. 2003 Dec;11(12):1513-20. PMID:14656435<ref>PMID:14656435</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-==Overview==
+</div>
-The protective antigen (PA) moiety of anthrax toxin transports edema factor and lethal factor to the cytosol of mammalian cells by a mechanism that depends on its ability to oligomerize and form pores in the endosomal membrane. Previously, some mutated forms of PA, designated dominant negative (DN), were found to coassemble with wild-type PA and generate defective heptameric pore-precursors (prepores). Prepores containing DN-PA are impaired in pore formation and in translocating edema factor and lethal factor across the endosomal membrane. To create a more comprehensive map of sites within PA where a single amino acid replacement can give a DN phenotype, we used automated systems to generate a Cys-replacement mutation for each of the 568 residues of PA63, the active 63-kDa proteolytic fragment of PA. Thirty-three mutations that reduced PA's ability to mediate toxicity at least 100-fold were identified in all four domains of PA63. A majority (22) were in domain 2, the pore-forming domain. Seven of the domain-2 mutations, located in or adjacent to the 2beta6 strand, the 2beta7 strand, and the 2beta10-2beta11 loop, gave the DN phenotype. This study demonstrates the feasibility of high-throughput scanning mutagenesis of a moderate sized protein. The results show that DN mutations cluster in a single domain and implicate 2beta6 and 2beta7 strands and the 2beta10-2beta11 loop in the conformational rearrangement of the prepore to the pore. They also add to the repertoire of mutations available for structure-function studies and for designing new antitoxic agents for treatment of anthrax.
+<div class="pdbe-citations 1rj7" style="background-color:#fffaf0;"></div>
+== References ==
-==Disease==
+<references/>
-Known diseases associated with this structure: Ectodermal dysplasia-1, anhidrotic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300451 300451]], Hypodontia, X-linked OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300451 300451]]
+__TOC__
+</StructureSection>
-==About this Structure==
-RJ7 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=1RJ7 OCA].
-==Reference==
-Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis., Mourez M, Yan M, Lacy DB, Dillon L, Bentsen L, Marpoe A, Maurin C, Hotze E, Wigelsworth D, Pimental RA, Ballard JD, Collier RJ, Tweten RK, Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13803-8. Epub 2003 Nov 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14623961 14623961]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Ackerly, H.]]
+[[Category: Ackerly H]]
-[[Category: Compaan, D M.]]
+[[Category: Compaan DM]]
-[[Category: Dixit, V M.]]
+[[Category: Dixit VM]]
-[[Category: Hymowitz, S G.]]
+[[Category: Hymowitz SG]]
-[[Category: Starovasnik, M A.]]
+[[Category: Starovasnik MA]]
-[[Category: Vos, A M.de.]]
+[[Category: Yan M]]
-[[Category: Yan, M.]]
+[[Category: De Vos AM]]
-[[Category: beta-bulge]]
-[[Category: eda]]
-[[Category: morphogen]]
-[[Category: tnf]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:52:19 2008''