6sit | pdb_00006sit
Pseudo-atomic crystal structure of the desmoglein 2 - human adenovirus serotype 3 fibre knob complex
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. Publication Abstract from PubMedThe 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
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