6LSA

Complex structure of bovine herpesvirus 1 glycoprotein D and bovine nectin-1 IgV

6LSA の概要

• エントリーDOI: 10.2210/pdb6lsa/pdb
• 分子名称: Nectin cell adhesion molecule 1, Envelope glycoprotein D, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: complex structure, viral protein
• 由来する生物種: Bos taurus (Bovine); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 94811.60

構造登録者

Yue, D.,Chen, Z.J.,Yang, F.L.,Ye, F.,Lin, S.,Cheng, Y.W.,Wang, J.C.,Chen, Z.M.,Lin, X.,Yang, J.,Chen, H.,Zhang, Z.L.,You, Y.,Sun, H.L.,Wen, A.,Wang, L.L.,Zheng, Y.,Cao, Y.,Li, Y.H.,Lu, G.W. (登録日: 2020-01-17, 公開日: 2020-06-17, 最終更新日: 2024-10-23)

主引用文献

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.
Crystal structure of bovine herpesvirus 1 glycoprotein D bound to nectin-1 reveals the basis for its low-affinity binding to the receptor.
Sci Adv, 6:eaba5147-eaba5147, 2020

PubMed Abstract: 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.

PubMed: 32426511
DOI: 10.1126/sciadv.aba5147

実験手法

X-RAY DIFFRACTION (2.204 Å)