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The Sequence Basis for Selectivity of Ephrin-B2 for Eph Receptors and Pathogenic Henipavirus G Glycoproteins [EFNB2 DEEP MUTAGENESIS]

ABSTRACT: Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and also functions as a cell entry receptor for several henipaviruses, which are zoonotic viruses with pandemic potential. Two such viruses, Nipah (NiV) and Hendra (HeV), are highly pathogenic in humans yet do not have any widely approved virus-specific therapeutics or vaccines. Soluble Fc-fusions of EFNB2 (sEFNB2-Fc) are known to bind the attachment glycoprotein G of both viruses and inhibit viral infection of cells. However, the potential of sEFNB2-Fc as a neutralizing agent in vivo is hindered by its binding activity to native Eph receptors. Therefore, using deep mutagenesis, variants of EFNB2 at cell surface are identified with increased binding to the soluble head domain of NiV-G over soluble Fc-fusions of the extracellular domains of Eph receptors. Specificity mutations for NiV-G are found primarily at the binding interface, especially around the G-H binding loop. The mutational landscape offers a preliminary blueprint for engineering sEFNB2-Fc variants with high specificity and affinity for potent neutralization of henipaviruses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234213 | GEO | 2023/06/12

REPOSITORIES: GEO

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The Sequence Basis for Selectivity of Ephrin-B2 for Eph Receptors and Pathogenic Henipavirus G Glycoproteins [EFNB2-D62Q DEEP MUTAGENESIS]

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