8ZHW

Structure of Mokola lyssavirus glycoprotein in post-fusion state

Summary for 8ZHW

• Entry DOI: 10.2210/pdb8zhw/pdb
• Descriptor: Glycoprotein (1 entity in total)
• Functional Keywords: glycoprotein, lyssavirus, membrane fusion, virus, viral protein
• Biological source: Lyssavirus mokola; More
• Total number of polymer chains: 3
• Total formula weight: 147344.79

Authors

Lu, G.W.,Yang, F.L.,Lin, S.,Yang, J.,Ye, F. (deposition date: 2024-05-11, release date: 2025-02-05, Last modification date: 2025-08-20)

Primary citation

Yang, F.,Lin, S.,Yuan, X.,Shu, S.,Yu, Y.,Yang, J.,Ye, F.,Chen, Z.,He, B.,Li, J.,Zhao, Q.,Ye, H.,Cao, Y.,Lu, G.
Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease.
Plos Pathog., 21:e1012923-e1012923, 2025

PubMed Abstract: Lyssavirus glycoprotein plays a crucial role in mediating virus entry and serves as the major target for neutralizing antibodies. During membrane fusion, the lyssavirus glycoprotein undergoes a series of low-pH-induced conformational transitions. Here, we report the structures of Ikoma lyssavirus and Mokola lyssavirus glycoproteins, with which we believe that we have trapped the proteins in pre-fusion and post-fusion states respectively. By analyzing the available lyssaviral glycoprotein structures, we present a sequential conformation-transition model, in which two structural elements in the glycoprotein undergo fine-modulated secondary structural transitions, changing the glycoprotein from a bended hairpin conformation to an extended linear conformation. In addition, such conformational change is further facilitated, as observed in our surface plasmon resonance assay, by the pH-regulated interactions between the membrane-proximal region and the pleckstrin homology and the fusion domains. The structural features elucidated in this study will facilitate the design of vaccines and anti-viral drugs against lyssaviruses.

PubMed: 39970183
DOI: 10.1371/journal.ppat.1012923

Experimental method

X-RAY DIFFRACTION (3.199 Å)