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Publication Abstract from PubMed

Bovine herpesvirus 1 (BHV-1) has received increasing attention for its potential oncolytic applications. BHV-1 recognizes nectin-1 for cell entry via viral glycoprotein D (gD) but represents a low-affinity nectin-1 binding virus. The molecular basis underlying this low receptor-binding affinity, however, remains unknown. Here, the crystal structures of BHV-1 gD in the free and nectin-1-bound forms are presented. While showing an overall resembled nectin-1 binding mode to other alphaherpesvirus gDs, BHV-1 gD has a unique G-strand/alpha2-helix interloop that disturbs gD/nectin-1 interactions. Residue R188 residing in this loop is observed to otherwise cause strong steric hindrance with the bound receptor, making a large conformational change of the loop a prerequisite for nectin-1 engagement. Subsequently, substitution of R188 with glycine markedly enhances the affinity of the BHV-1-gD/nectin-1 interaction (by about fivefold). These structural and functional data delineate the receptor-recognition basis for BHV-1, which might facilitate BHV-1-based oncolytic design in the future.

Crystal structure of bovine herpesvirus 1 glycoprotein D bound to nectin-1 reveals the basis for its low-affinity binding to the receptor.,Yue D, Chen Z, Yang F, Ye F, Lin S, He B, Cheng Y, Wang J, Chen Z, Lin X, Yang J, Chen H, Zhang Z, You Y, Sun H, Wen A, Wang L, Zheng Y, Cao Y, Li Y, Lu G Sci Adv. 2020 May 13;6(20):eaba5147. doi: 10.1126/sciadv.aba5147. eCollection, 2020 May. PMID:32426511^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.