PT - JOURNAL ARTICLE AU - Yue, Dan AU - Chen, Zhujun AU - Yang, Fanli AU - Ye, Fei AU - Lin, Sheng AU - He, Bin AU - Cheng, Yanwei AU - Wang, Jichao AU - Chen, Zimin AU - Lin, Xi AU - Yang, Jing AU - Chen, Hua AU - Zhang, Zhonglin AU - You, Yu AU - Sun, Honglu AU - Wen, Ao AU - Wang, Lingling AU - Zheng, Yue AU - Cao, Yu AU - Li, Yuhua AU - Lu, Guangwen TI - Crystal structure of bovine herpesvirus 1 glycoprotein D bound to nectin-1 reveals the basis for its low-affinity binding to the receptor AID - 10.1126/sciadv.aba5147 DP - 2020 May 01 TA - Science Advances PG - eaba5147 VI - 6 IP - 20 4099 - http://advances.sciencemag.org/content/6/20/eaba5147.short 4100 - http://advances.sciencemag.org/content/6/20/eaba5147.full SO - Sci Adv2020 May 01; 6 AB - 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/α2-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.