8YG6

The pre-fusion structure of baculovirus fusion protein GP64

Summary for 8YG6

• Entry DOI: 10.2210/pdb8yg6/pdb
• EMDB information: 39237
• Related PRD ID: PRD_900017
• Descriptor: Major envelope glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: structural protein
• Biological source: Autographa californica nucleopolyhedrovirus
• Total number of polymer chains: 3
• Total formula weight: 163890.27

Authors

Du, D.,Guo, J.,Li, S. (deposition date: 2024-02-26, release date: 2024-09-11, Last modification date: 2024-10-30)

Primary citation

Guo, J.,Li, S.,Bai, L.,Zhao, H.,Shang, W.,Zhong, Z.,Maimaiti, T.,Gao, X.,Ji, N.,Chao, Y.,Li, Z.,Du, D.
Structural transition of GP64 triggered by a pH-sensitive multi-histidine switch.
Nat Commun, 15:7668-7668, 2024

PubMed Abstract: The fusion of viruses with cellular membranes is a critical step in the life cycle of enveloped viruses. This process is facilitated by viral fusion proteins, many of which are conformationally pH-sensitive. The specifics of how changes in pH initiate this fusion have remained largely elusive. This study presents the cryo-electron microscopy (cryo-EM) structures of a prototype class III fusion protein, GP64, in its prefusion and early intermediate states, revealing the structural intermediates accompanying the membrane fusion process. The structures identify the involvement of a pH-sensitive switch, comprising H23, H245, and H304, in sensing the low pH that triggers the initial step of membrane fusion. The pH sensing role of this switch is corroborated by assays of cell-cell syncytium formation and dual dye-labeling. The findings demonstrate that coordination between multiple histidine residues acts as a pH sensor and activator. The involvement of a multi-histidine switch in viral fusion is applicable to fusogens of human-infecting thogotoviruses and other viruses, which could lead to strategies for developing anti-viral therapies and vaccines.

PubMed: 39227374
DOI: 10.1038/s41467-024-51799-4

Experimental method

ELECTRON MICROSCOPY (2.77 Å)