FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4367183904> ?p ?o ?g. }

• W4367183904 abstract "ABSTRACT Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and functions as a cell entry receptor for several henipaviruses including Nipah virus (NiV), a pathogenic zoonotic virus with pandemic potential. To understand the sequence basis of promiscuity for EFNB2 binding to the attachment glycoprotein of NiV (NiV-G) and Eph receptors, we performed deep mutagenesis on EFNB2 to identify mutations that enhance binding to NiV-G over EphB2, one of the highest affinity Eph receptors. The mutations highlight how different EFNB2 conformations are selected by NiV-G versus EphB2. Specificity mutations are enriched at the base of the G-H binding loop of EFNB2, especially surrounding a phenylalanine hinge upon which the G-H loop pivots, and at a phenylalanine hook that rotates away from the EFNB2 core to engage Eph receptors. One EFNB2 mutant, D62Q, possesses pan-specificity to the attachment glycoproteins of closely related henipaviruses and has markedly diminished binding to the six Eph receptors. However, EFNB2-D62Q has high residual binding to EphB3 and EphB4. A second deep mutational scan of EFNB2 identified combinatorial mutations to further enhance specificity to NiV-G. A triple mutant of soluble EFNB2, D62Q-Q130L-V167L, has minimal binding to Eph receptors but maintains binding, albeit reduced, to NiV-G. Soluble EFNB2 decoy receptors carrying the specificity mutations were potent neutralizers of chimeric henipaviruses. These findings demonstrate how specific residue changes at the shared binding interface of a promiscuous ligand (EFNB2) can influence selectivity for multiple receptors, and may also offer insight towards the development of henipavirus therapeutics and diagnostics. IMPORTANCE Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and regulates multiple cell developmental and signaling processes. It also functions as the cell entry receptor for Nipah virus and Hendra virus, zoonotic viruses that can cause respiratory and/or neurological symptoms in humans with high mortality. Here, we investigate the sequence basis of EFNB2 specificity for binding the Nipah virus attachment G glycoprotein over Eph receptors. We then use this information to engineer EFNB2 as a soluble decoy receptor that specifically binds the attachment glycoproteins of Nipah virus and other related henipaviruses to neutralize infection. These findings further mechanistic understanding of protein selectivity and may facilitate the development of diagnostics or therapeutics against henipavirus infection." @default.
• W4367183904 created "2023-04-28" @default.
• W4367183904 creator A5006321543 @default.
• W4367183904 creator A5011425090 @default.
• W4367183904 creator A5033036347 @default.
• W4367183904 creator A5037833018 @default.
• W4367183904 creator A5041481754 @default.
• W4367183904 creator A5053940473 @default.
• W4367183904 creator A5057104211 @default.
• W4367183904 creator A5058192670 @default.
• W4367183904 date "2023-04-26" @default.
• W4367183904 modified "2023-09-29" @default.
• W4367183904 title "The Sequence Basis for Selectivity of Ephrin-B2 Ligand for Eph Receptors and Pathogenic Henipavirus G Glycoproteins" @default.
• W4367183904 cites W1644209505 @default.
• W4367183904 cites W1921028801 @default.
• W4367183904 cites W1969347183 @default.
• W4367183904 cites W1974077634 @default.
• W4367183904 cites W1978118805 @default.
• W4367183904 cites W1984844573 @default.
• W4367183904 cites W1999267207 @default.
• W4367183904 cites W2001366186 @default.
• W4367183904 cites W2003680799 @default.
• W4367183904 cites W2007432440 @default.
• W4367183904 cites W2011937142 @default.
• W4367183904 cites W2012828294 @default.
• W4367183904 cites W2015937741 @default.
• W4367183904 cites W2018601378 @default.
• W4367183904 cites W2021540849 @default.
• W4367183904 cites W2026799512 @default.
• W4367183904 cites W2031550258 @default.
• W4367183904 cites W2032294909 @default.
• W4367183904 cites W2033604002 @default.
• W4367183904 cites W2050329907 @default.
• W4367183904 cites W2054288808 @default.
• W4367183904 cites W2060588922 @default.
• W4367183904 cites W2084935338 @default.
• W4367183904 cites W2093467487 @default.
• W4367183904 cites W2102800404 @default.
• W4367183904 cites W2112972263 @default.
• W4367183904 cites W2122500867 @default.
• W4367183904 cites W2129202771 @default.
• W4367183904 cites W2135708602 @default.
• W4367183904 cites W2141247392 @default.
• W4367183904 cites W2141674733 @default.
• W4367183904 cites W2145381994 @default.
• W4367183904 cites W2149291385 @default.
• W4367183904 cites W2160824865 @default.
• W4367183904 cites W2163393645 @default.
• W4367183904 cites W2164027317 @default.
• W4367183904 cites W2169515696 @default.
• W4367183904 cites W2607373410 @default.
• W4367183904 cites W2735047879 @default.
• W4367183904 cites W2757676953 @default.
• W4367183904 cites W2915069441 @default.
• W4367183904 cites W2923493950 @default.
• W4367183904 cites W2942013817 @default.
• W4367183904 cites W2949592035 @default.
• W4367183904 cites W2966727359 @default.
• W4367183904 cites W2991465206 @default.
• W4367183904 cites W2994981970 @default.
• W4367183904 cites W2999745427 @default.
• W4367183904 cites W3003639174 @default.
• W4367183904 cites W3011273722 @default.
• W4367183904 cites W3019096408 @default.
• W4367183904 cites W3035971441 @default.
• W4367183904 cites W3036957826 @default.
• W4367183904 cites W3047003416 @default.
• W4367183904 cites W3049427054 @default.
• W4367183904 cites W3084289412 @default.
• W4367183904 cites W3085213763 @default.
• W4367183904 cites W3126741775 @default.
• W4367183904 cites W3127842459 @default.
• W4367183904 cites W3130783125 @default.
• W4367183904 cites W3132966328 @default.
• W4367183904 cites W3149853056 @default.
• W4367183904 cites W3176871516 @default.
• W4367183904 cites W3198178314 @default.
• W4367183904 cites W3201961235 @default.
• W4367183904 cites W4200110347 @default.
• W4367183904 cites W4210724544 @default.
• W4367183904 cites W4212996660 @default.
• W4367183904 cites W4213371317 @default.
• W4367183904 cites W4220786646 @default.
• W4367183904 cites W4220869301 @default.
• W4367183904 cites W4220981600 @default.
• W4367183904 cites W4224241471 @default.
• W4367183904 cites W4229017063 @default.
• W4367183904 cites W4237880060 @default.
• W4367183904 cites W4251787227 @default.
• W4367183904 cites W4281555379 @default.
• W4367183904 cites W4283590984 @default.
• W4367183904 cites W4296553964 @default.
• W4367183904 cites W4300803799 @default.
• W4367183904 doi "https://doi.org/10.1101/2023.04.26.538420" @default.
• W4367183904 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37162958" @default.
• W4367183904 hasPublicationYear "2023" @default.
• W4367183904 type Work @default.
• W4367183904 citedByCount "0" @default.
• W4367183904 crossrefType "posted-content" @default.
• W4367183904 hasAuthorship W4367183904A5006321543 @default.

• next