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.