2wbw

Ad37 fibre head in complex with CAR D1 and sialic acid

spinqualitylabelsall models 2wbw, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wbw is a 2 chain structure with sequence from Homo sapiens and Human adenovirus D37. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: CA, SIA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q64823_9ADEN Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad-erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a mechanism that may explain the biodistribution and pathogenic inconsistencies found between human and animal models. The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution.,Seiradake E, Henaff D, Wodrich H, Billet O, Perreau M, Hippert C, Mennechet F, Schoehn G, Lortat-Jacob H, Dreja H, Ibanes S, Kalatzis V, Wang JP, Finberg RW, Cusack S, Kremer EJ PLoS Pathog. 2009 Jan;5(1):e1000277. Epub 2009 Jan 2. PMID:19119424 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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