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Human herpesvirus 8 molecular mimicry of ephrin ligands facilitates cell entry and triggers EphA2 signaling

PLoS Biol. 2021-09; 
Taylor P Light, Delphine Brun, Pablo Guardado-Calvo, Riccardo Pederzoli, Ahmed Haouz, Frank Neipel, Félix A Rey, Kalina Hristova, Marija Backovic
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Custom Vector Construction … To avoid lengthy selection of the stably transfected S2 cells expressing recombinant proteins (4-5 646 weeks), a panel of gH/gL and EphA2 variants to be tested in biophysical assays was ordered as synthetic 647 genes (GenScript) cloned in pcDNA3.1 (+) vector for transient … Get A Quote

摘要

Human herpesvirus 8 (HHV-8) is an oncogenic virus that enters cells by fusion of the viral and endosomal cellular membranes in a process mediated by viral surface glycoproteins. One of the cellular receptors hijacked by HHV-8 to gain access to cells is the EphA2 tyrosine kinase receptor, and the mechanistic basis of EphA2-mediated viral entry remains unclear. Using X-ray structure analysis, targeted mutagenesis, and binding studies, we here show that the HHV-8 envelope glycoprotein complex H and L (gH/gL) binds with subnanomolar affinity to EphA2 via molecular mimicry of the receptor's cellular ligands, ephrins (Eph family receptor interacting proteins), revealing a pivotal role for the conserved gH residue E52... More

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