1rj8: Difference between revisions

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<StructureSection load='1rj8' size='340' side='right'caption='[[1rj8]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
<StructureSection load='1rj8' size='340' side='right'caption='[[1rj8]], [[Resolution|resolution]] 2.23&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1rj8]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1RJ8 FirstGlance]. <br>
<table><tr><td colspan='2'>[[1rj8]] is a 6 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=1RJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RJ8 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1rj7|1rj7]]</div></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]] 2.23&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EDA gene, splice form EDA-A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rj8 OCA], [https://pdbe.org/1rj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rj8 RCSB], [https://www.ebi.ac.uk/pdbsum/1rj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rj8 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1rj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rj8 OCA], [http://pdbe.org/1rj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1rj8 RCSB], [http://www.ebi.ac.uk/pdbsum/1rj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1rj8 ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/EDA_HUMAN EDA_HUMAN]] Defects in EDA are the cause of ectodermal dysplasia 1, hypohidrotic, X-linked (XHED) [MIM:[http://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:[http://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>
[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 ==
== Function ==
[[http://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.  
[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 ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1rj8 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=1rj8 ConSurf].
<div style="clear:both"></div>
<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.
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>
</div>
<div class="pdbe-citations 1rj8" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[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: Hormone-growth factor complex]]
[[Category: Jelly roll]]
[[Category: Splice variant]]
[[Category: Tnf domain]]
[[Category: Trimer]]

Latest revision as of 09:12, 3 April 2024

The crystal structure of TNF family member EDA-A2The crystal structure of TNF family member EDA-A2

Structural highlights

1rj8 is a 6 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 2.23Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

EDA_HUMAN Defects in EDA are the cause of ectodermal dysplasia 1, hypohidrotic, X-linked (XHED) [MIM: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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] Defects in EDA are the cause of tooth agenesis selective X-linked type 1 (STHAGX1) [MIM: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).[24] [25]

Function

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

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

References

  1. ↑ Kere J, Srivastava AK, Montonen O, Zonana J, Thomas N, Ferguson B, Munoz F, Morgan D, Clarke A, Baybayan P, Chen EY, Ezer S, Saarialho-Kere U, de la Chapelle A, Schlessinger D. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein. Nat Genet. 1996 Aug;13(4):409-16. PMID:8696334 doi:10.1038/ng0895-409
  2. ↑ Monreal AW, Zonana J, Ferguson B. Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations. Am J Hum Genet. 1998 Aug;63(2):380-9. PMID:9683615 doi:S0002-9297(07)61481-5
  3. ↑ Bayes M, Hartung AJ, Ezer S, Pispa J, Thesleff I, Srivastava AK, Kere J. The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative splicing and encodes ectodysplasin-A with deletion mutations in collagenous repeats. Hum Mol Genet. 1998 Oct;7(11):1661-9. PMID:9736768
  4. ↑ Elomaa O, Pulkkinen K, Hannelius U, Mikkola M, Saarialho-Kere U, Kere J. Ectodysplasin is released by proteolytic shedding and binds to the EDAR protein. Hum Mol Genet. 2001 Apr 15;10(9):953-62. PMID:11309369
  5. ↑ Chen Y, Molloy SS, Thomas L, Gambee J, Bachinger HP, Ferguson B, Zonana J, Thomas G, Morris NP. Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7218-23. PMID:11416205 doi:10.1073/pnas.131076098
  6. ↑ Hertz JM, Norgaard Hansen K, Juncker I, Kjeldsen M, Gregersen N. A novel missense mutation (402C-->T) in exon 1 in the EDA gene in a family with X-linked hypohidrotic ectodermal dysplasia. Clin Genet. 1998 Mar;53(3):205-9. PMID:9630076
  7. ↑ Ferguson BM, Thomas NS, Munoz F, Morgan D, Clarke A, Zonana J. Scarcity of mutations detected in families with X linked hypohidrotic ectodermal dysplasia: diagnostic implications. J Med Genet. 1998 Feb;35(2):112-5. PMID:9507389
  8. ↑ Martinez F, Millan JM, Orellana C, Prieto F. X-linked anhidrotic (hypohidrotic) ectodermal dysplasia caused by a novel mutation in EDA1 gene: 406T > G (Leu55Arg) J Invest Dermatol. 1999 Aug;113(2):285-6. PMID:10469321 doi:10.1046/j.1523-1747.1999.00656.x
  9. ↑ Aoki N, Ito K, Tachibana T, Ito M. A novel arginine-->Serine mutation in EDA1 in a Japanese family with X-linked anhidrotic ectodermal dysplasia. J Invest Dermatol. 2000 Aug;115(2):329-30. PMID:10951256 doi:10.1046/j.1523-1747.2000.00065-1.x
  10. ↑ Kobielak K, Kobielak A, Roszkiewicz J, Wierzba J, Limon J, Trzeciak WH. Mutations in the EDA gene in three unrelated families reveal no apparent correlation between phenotype and genotype in the patients with an X-linked anhidrotic ectodermal dysplasia. Am J Med Genet. 2001 May 1;100(3):191-7. PMID:11343303
  11. ↑ Vincent MC, Biancalana V, Ginisty D, Mandel JL, Calvas P. Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia. Eur J Hum Genet. 2001 May;9(5):355-63. PMID:11378824 doi:10.1038/sj.ejhg.5200635
  12. ↑ Paakkonen K, Cambiaghi S, Novelli G, Ouzts LV, Penttinen M, Kere J, Srivastava AK. The mutation spectrum of the EDA gene in X-linked anhidrotic ectodermal dysplasia. Hum Mutat. 2001 Apr;17(4):349. PMID:11295832 doi:10.1002/humu.33
  13. ↑ Schneider P, Street SL, Gaide O, Hertig S, Tardivel A, Tschopp J, Runkel L, Alevizopoulos K, Ferguson BM, Zonana J. Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect three major functional domains in the tumor necrosis factor family member ectodysplasin-A. J Biol Chem. 2001 Jun 1;276(22):18819-27. Epub 2001 Mar 14. PMID:11279189 doi:10.1074/jbc.M101280200
  14. ↑ Vincent MC, Cossee M, Vabres P, Stewart F, Bonneau D, Calvas P. Pitfalls in clinical diagnosis of female carriers of X-linked hypohidrotic ectodermal dysplasia. Arch Dermatol. 2002 Sep;138(9):1256-8. PMID:12225002
  15. ↑ Hsu MM, Chao SC, Lu AC. A novel missense mutation (Gln306His) in exon 7 of the ED1 gene causing anhidrotic ectodermal dysplasia with prominent milia-like facial sebaceous papules. Br J Dermatol. 2003 Aug;149(2):443-5. PMID:12932274
  16. ↑ Tarpey P, Pemberton TJ, Stockton DW, Das P, Ninis V, Edkins S, Andrew Futreal P, Wooster R, Kamath S, Nayak R, Stratton MR, Patel PI. A novel Gln358Glu mutation in ectodysplasin A associated with X-linked dominant incisor hypodontia. Am J Med Genet A. 2007 Feb 15;143(4):390-4. PMID:17256800 doi:10.1002/ajmg.a.31567
  17. ↑ van der Hout AH, Oudesluijs GG, Venema A, Verheij JB, Mol BG, Rump P, Brunner HG, Vos YJ, van Essen AJ. Mutation screening of the Ectodysplasin-A receptor gene EDAR in hypohidrotic ectodermal dysplasia. Eur J Hum Genet. 2008 Jun;16(6):673-9. Epub 2008 Jan 30. PMID:18231121 doi:5202012
  18. ↑ Shimomura Y, Wajid M, Weiser J, Kraemer L, Ishii Y, Lombillo V, Bale SJ, Christiano AM. Identification of mutations in the EDA and EDAR genes in Pakistani families with hypohidrotic ectodermal dysplasia. Clin Genet. 2009 Jun;75(6):582-4. doi: 10.1111/j.1399-0004.2009.01178.x. Epub, 2009 May 5. PMID:19438931 doi:10.1111/j.1399-0004.2009.01178.x
  19. ↑ Gunadi, Miura K, Ohta M, Sugano A, Lee MJ, Sato Y, Matsunaga A, Hayashi K, Horikawa T, Miki K, Wataya-Kaneda M, Katayama I, Nishigori C, Matsuo M, Takaoka Y, Nishio H. Two novel mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia. Pediatr Res. 2009 Apr;65(4):453-7. doi: 10.1203/PDR.0b013e3181991229. PMID:19127222 doi:10.1203/PDR.0b013e3181991229
  20. ↑ Khabour OF, Mesmar FS, Al-Tamimi F, Al-Batayneh OB, Owais AI. Missense mutation of the EDA gene in a Jordanian family with X-linked hypohidrotic ectodermal dysplasia: phenotypic appearance and speech problems. Genet Mol Res. 2010 May 18;9(2):941-8. doi: 10.4238/vol9-2gmr810. PMID:20486090 doi:10.4238/vol9-2gmr810
  21. ↑ Cluzeau C, Hadj-Rabia S, Jambou M, Mansour S, Guigue P, Masmoudi S, Bal E, Chassaing N, Vincent MC, Viot G, Clauss F, Maniere MC, Toupenay S, Le Merrer M, Lyonnet S, Cormier-Daire V, Amiel J, Faivre L, de Prost Y, Munnich A, Bonnefont JP, Bodemer C, Smahi A. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum Mutat. 2011 Jan;32(1):70-2. doi: 10.1002/humu.21384. PMID:20979233 doi:10.1002/humu.21384
  22. ↑ Liu Y, Yu X, Wang L, Li C, Archacki S, Huang C, Liu JY, Wang Q, Liu M, Tang Z. Mutation p.Leu354Pro in EDA causes severe hypohidrotic ectodermal dysplasia in a Chinese family. Gene. 2012 Jan 10;491(2):246-50. doi: 10.1016/j.gene.2011.10.009. Epub 2011 Oct, 10. PMID:22008666 doi:10.1016/j.gene.2011.10.009
  23. ↑ Piccione M, Serra G, Sanfilippo C, Andreucci E, Sani I, Corsello G. A new mutation in EDA gene in X-linked hypohidrotic ectodermal dysplasia associated with keratoconus. Minerva Pediatr. 2012 Feb;64(1):59-64. PMID:22350046
  24. ↑ Tao R, Jin B, Guo SZ, Qing W, Feng GY, Brooks DG, Liu L, Xu J, Li T, Yan Y, He L. A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia. J Hum Genet. 2006;51(5):498-502. Epub 2006 Apr 1. PMID:16583127 doi:10.1007/s10038-006-0389-2
  25. ↑ Han D, Gong Y, Wu H, Zhang X, Yan M, Wang X, Qu H, Feng H, Song S. Novel EDA mutation resulting in X-linked non-syndromic hypodontia and the pattern of EDA-associated isolated tooth agenesis. Eur J Med Genet. 2008 Nov-Dec;51(6):536-46. doi: 10.1016/j.ejmg.2008.06.002. Epub, 2008 Jul 9. PMID:18657636 doi:10.1016/j.ejmg.2008.06.002

1rj8, resolution 2.23Å

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