6qnt

Structural highlights

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.

See Also

• Cadherin 3D structures

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, Effantin G, Zubieta C, Burmeister W, Iseni F, Wang H, Lieber A, Schoehn G, Fender P. CryoEM structure of adenovirus type 3 fibre with desmoglein 2 shows an unusual mode of receptor engagement. Nat Commun. 2019 Mar 12;10(1):1181. doi: 10.1038/s41467-019-09220-y. PMID:30862836 doi:http://dx.doi.org/10.1038/s41467-019-09220-y