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'''Unreleased structure'''


The entry 6sit is ON HOLD until Paper Publication
==Pseudo-atomic crystal structure of the desmoglein 2 - human adenovirus serotype 3 fibre knob complex==
<StructureSection load='6sit' size='340' side='right'caption='[[6sit]], [[Resolution|resolution]] 4.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6sit]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SIT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6qnt|6qnt]], [[6qnu|6qnu]], [[5erd|5erd]]</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=6sit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sit OCA], [http://pdbe.org/6sit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sit RCSB], [http://www.ebi.ac.uk/pdbsum/6sit PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sit 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>  
== Function ==
[[http://www.uniprot.org/uniprot/SPIKE_ADE03 SPIKE_ADE03]] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CD46 to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Heparan sulfate might also play a role in virus binding. [[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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cryo-electron microscopy (cryo-EM) structure of the complex between the trimeric human adenovirus B serotype 3 fibre knob and human desmoglein 2 fragments containing cadherin domains EC2 and EC3 has been published, showing 3:1 and 3:2 complexes. Here, the crystal structure determined at 4.5 A resolution is presented with one EC2-EC3 desmoglein fragment bound per fibre knob monomer in the asymmetric unit, leading to an apparent 3:3 stoichiometry. However, in concentrated solution the 3:2 complex is predominant, as shown by small-angle X-ray scattering (SAXS), while cryo-EM at lower concentrations showed a majority of the 3:1 complex. Substitution of the calcium ions bound to the desmoglein domains by terbium ions allowed confirmation of the X-ray model using their anomalous scattering and shows that at least one binding site per cluster of calcium ions is intact and exchangeable and, combined with SAXS data, that the cadherin domains are folded even in the distal part that is invisible in the cryo-EM reconstruction.


Authors: Burmeister, W.P., Fender, P., Vassal-Stermann, E.
Intermediate-resolution crystal structure of the human adenovirus B serotype 3 fibre knob in complex with the EC2-EC3 fragment of desmoglein 2.,Vassal-Stermann E, Hutin S, Fender P, Burmeister WP Acta Crystallogr F Struct Biol Commun. 2019 Dec 1;75(Pt 12):750-757. doi:, 10.1107/S2053230X19015784. Epub 2019 Nov 27. PMID:31797817<ref>PMID:31797817</ref>


Description: Pseudo-atomic crystal structure of the desmoglein 2 -human adenovirus serotype 3 fibre knob complex
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 6sit" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Burmeister, W P]]
[[Category: Fender, P]]
[[Category: Vassal-Stermann, E]]
[[Category: Vassal-Stermann, E]]
[[Category: Fender, P]]
[[Category: Cell surface glycoprotein]]
[[Category: Burmeister, W.P]]
[[Category: Desmosome]]
[[Category: Extracellular domain]]
[[Category: Viral protein]]
[[Category: Virus receptor]]

Revision as of 10:55, 18 December 2019

Pseudo-atomic crystal structure of the desmoglein 2 - human adenovirus serotype 3 fibre knob complexPseudo-atomic crystal structure of the desmoglein 2 - human adenovirus serotype 3 fibre knob complex

Structural highlights

6sit is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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

[SPIKE_ADE03] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host receptor CD46 to provide virion initial attachment to target cell. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Heparan sulfate might also play a role in virus binding. [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

The cryo-electron microscopy (cryo-EM) structure of the complex between the trimeric human adenovirus B serotype 3 fibre knob and human desmoglein 2 fragments containing cadherin domains EC2 and EC3 has been published, showing 3:1 and 3:2 complexes. Here, the crystal structure determined at 4.5 A resolution is presented with one EC2-EC3 desmoglein fragment bound per fibre knob monomer in the asymmetric unit, leading to an apparent 3:3 stoichiometry. However, in concentrated solution the 3:2 complex is predominant, as shown by small-angle X-ray scattering (SAXS), while cryo-EM at lower concentrations showed a majority of the 3:1 complex. Substitution of the calcium ions bound to the desmoglein domains by terbium ions allowed confirmation of the X-ray model using their anomalous scattering and shows that at least one binding site per cluster of calcium ions is intact and exchangeable and, combined with SAXS data, that the cadherin domains are folded even in the distal part that is invisible in the cryo-EM reconstruction.

Intermediate-resolution crystal structure of the human adenovirus B serotype 3 fibre knob in complex with the EC2-EC3 fragment of desmoglein 2.,Vassal-Stermann E, Hutin S, Fender P, Burmeister WP Acta Crystallogr F Struct Biol Commun. 2019 Dec 1;75(Pt 12):750-757. doi:, 10.1107/S2053230X19015784. Epub 2019 Nov 27. PMID:31797817[6]

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

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ Vassal-Stermann E, Hutin S, Fender P, Burmeister WP. Intermediate-resolution crystal structure of the human adenovirus B serotype 3 fibre knob in complex with the EC2-EC3 fragment of desmoglein 2. Acta Crystallogr F Struct Biol Commun. 2019 Dec 1;75(Pt 12):750-757. doi:, 10.1107/S2053230X19015784. Epub 2019 Nov 27. PMID:31797817 doi:http://dx.doi.org/10.1107/S2053230X19015784

6sit, resolution 4.50Å

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