5erd

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human Desmoglein-2 ectodomain

Structural highlights

5erd 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.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

DSG2_HUMAN Defects in DSG2 are the cause of familial arrhythmogenic right ventricular dysplasia type 10 (ARVD10) [MIM:610193; also known as arrhythmogenic right ventricular cardiomyopathy 10 (ARVC10). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.^[1] ^[2] ^[3] ^[4] Genetic variations in DSG2 are the cause of susceptibility to cardiomyopathy dilated type 1BB (CMD1BB) [MIM:612877. A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.^[5]

Function

DSG2_HUMAN Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.

Publication Abstract from PubMed

Desmosomes are intercellular adhesive junctions that impart strength to vertebrate tissues. Their dense, ordered intercellular attachments are formed by desmogleins (Dsgs) and desmocollins (Dscs), but the nature of trans-cellular interactions between these specialized cadherins is unclear. Here, using solution biophysics and coated-bead aggregation experiments, we demonstrate family-wise heterophilic specificity: All Dsgs form adhesive dimers with all Dscs, with affinities characteristic of each Dsg:Dsc pair. Crystal structures of ectodomains from Dsg2 and Dsg3 and from Dsc1 and Dsc2 show binding through a strand-swap mechanism similar to that of homophilic classical cadherins. However, conserved charged amino acids inhibit Dsg:Dsg and Dsc:Dsc interactions by same-charge repulsion and promote heterophilic Dsg:Dsc interactions through opposite-charge attraction. These findings show that Dsg:Dsc heterodimers represent the fundamental adhesive unit of desmosomes and provide a structural framework for understanding desmosome assembly.

Structural basis of adhesive binding by desmocollins and desmogleins.,Harrison OJ, Brasch J, Lasso G, Katsamba PS, Ahlsen G, Honig B, Shapiro L Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7160-5. doi:, 10.1073/pnas.1606272113. Epub 2016 Jun 13. PMID:27298358^[6]

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

References

↑ Awad MM, Dalal D, Cho E, Amat-Alarcon N, James C, Tichnell C, Tucker A, Russell SD, Bluemke DA, Dietz HC, Calkins H, Judge DP. DSG2 mutations contribute to arrhythmogenic right ventricular dysplasia/cardiomyopathy. Am J Hum Genet. 2006 Jul;79(1):136-42. Epub 2006 Apr 28. PMID:16773573 doi:10.1086/504393
↑ den Haan AD, Tan BY, Zikusoka MN, Llado LI, Jain R, Daly A, Tichnell C, James C, Amat-Alarcon N, Abraham T, Russell SD, Bluemke DA, Calkins H, Dalal D, Judge DP. Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Cardiovasc Genet. 2009 Oct;2(5):428-35. doi:, 10.1161/CIRCGENETICS.109.858217. Epub 2009 Jun 3. PMID:20031617 doi:10.1161/CIRCGENETICS.109.858217
↑ Barahona-Dussault C, Benito B, Campuzano O, Iglesias A, Leung TL, Robb L, Talajic M, Brugada R. Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Clin Genet. 2010 Jan;77(1):37-48. doi: 10.1111/j.1399-0004.2009.01282.x. Epub, 2009 Oct 15. PMID:19863551 doi:10.1111/j.1399-0004.2009.01282.x
↑ Gehmlich K, Syrris P, Peskett E, Evans A, Ehler E, Asimaki A, Anastasakis A, Tsatsopoulou A, Vouliotis AI, Stefanadis C, Saffitz JE, Protonotarios N, McKenna WJ. Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations. Cardiovasc Res. 2011 Apr 1;90(1):77-87. doi: 10.1093/cvr/cvq353. Epub 2010 Nov 9. PMID:21062920 doi:10.1093/cvr/cvq353
↑ Posch MG, Posch MJ, Geier C, Erdmann B, Mueller W, Richter A, Ruppert V, Pankuweit S, Maisch B, Perrot A, Buttgereit J, Dietz R, Haverkamp W, Ozcelik C. A missense variant in desmoglein-2 predisposes to dilated cardiomyopathy. Mol Genet Metab. 2008 Sep-Oct;95(1-2):74-80. doi: 10.1016/j.ymgme.2008.06.005., Epub 2008 Aug 3. PMID:18678517 doi:10.1016/j.ymgme.2008.06.005
↑ Harrison OJ, Brasch J, Lasso G, Katsamba PS, Ahlsen G, Honig B, Shapiro L. Structural basis of adhesive binding by desmocollins and desmogleins. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7160-5. doi:, 10.1073/pnas.1606272113. Epub 2016 Jun 13. PMID:27298358 doi:http://dx.doi.org/10.1073/pnas.1606272113

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5erd"

Categories: Homo sapiens | Large Structures | Brasch J | Harrison OJ | Shapiro L

@@ Line 3: / Line 3: @@
 <StructureSection load='5erd' size='340' side='right'caption='[[5erd]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5erd]] is a 2 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=5ERD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ERD FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5erd]] 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=5ERD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ERD FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5eqx|5eqx]], [[5erp|5erp]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DSG2, CDHF5 ([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=5erd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5erd OCA], [https://pdbe.org/5erd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5erd RCSB], [https://www.ebi.ac.uk/pdbsum/5erd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5erd ProSAT]</span></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=5erd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5erd OCA], [http://pdbe.org/5erd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5erd RCSB], [http://www.ebi.ac.uk/pdbsum/5erd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5erd ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/DSG2_HUMAN DSG2_HUMAN]] Defects in DSG2 are the cause of familial arrhythmogenic right ventricular dysplasia type 10 (ARVD10) [MIM:[http://omim.org/entry/610193 610193]]; also known as arrhythmogenic right ventricular cardiomyopathy 10 (ARVC10). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.<ref>PMID:16773573</ref> <ref>PMID:20031617</ref> <ref>PMID:19863551</ref> <ref>PMID:21062920</ref>   Genetic variations in DSG2 are the cause of susceptibility to cardiomyopathy dilated type 1BB (CMD1BB) [MIM:[http://omim.org/entry/612877 612877]]. A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18678517</ref>
+[https://www.uniprot.org/uniprot/DSG2_HUMAN DSG2_HUMAN] Defects in DSG2 are the cause of familial arrhythmogenic right ventricular dysplasia type 10 (ARVD10) [MIM:[https://omim.org/entry/610193 610193]; also known as arrhythmogenic right ventricular cardiomyopathy 10 (ARVC10). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.<ref>PMID:16773573</ref> <ref>PMID:20031617</ref> <ref>PMID:19863551</ref> <ref>PMID:21062920</ref>   Genetic variations in DSG2 are the cause of susceptibility to cardiomyopathy dilated type 1BB (CMD1BB) [MIM:[https://omim.org/entry/612877 612877]. A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18678517</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/DSG2_HUMAN DSG2_HUMAN]] Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
+[https://www.uniprot.org/uniprot/DSG2_HUMAN DSG2_HUMAN] Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 29: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Brasch, J]]
+[[Category: Brasch J]]
-[[Category: Harrison, O J]]
+[[Category: Harrison OJ]]
-[[Category: Shapiro, L]]
+[[Category: Shapiro L]]
-[[Category: Cell adhesion]]
-[[Category: Cell surface]]
-[[Category: Desmosome]]
-[[Category: Extracellular cadherin domain]]

5erd

From Proteopedia

Current revision

Crystal structure of human Desmoglein-2 ectodomain

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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