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TitleStructural transition of GP64 triggered by a pH-sensitive multi-histidine switch.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 7668, Year 2024
Publish dateSep 3, 2024
AuthorsJinliang Guo / Shangrong Li / Lisha Bai / Huimin Zhao / Wenyu Shang / Zhaojun Zhong / Tuerxunjiang Maimaiti / Xueyan Gao / Ning Ji / Yanjie Chao / Zhaofei Li / Dijun Du /
PubMed AbstractThe 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- ...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.
External linksNat Commun / PubMed:39227374 / PubMed Central
MethodsEM (single particle)
Resolution2.77 - 2.97 Å
Structure data

EMDB-39237, PDB-8yg6:
The pre-fusion structure of baculovirus fusion protein GP64
Method: EM (single particle) / Resolution: 2.77 Å

EMDB-39238, PDB-8yg8:
The early intermediate structure of baculovirus fusion protein GP64
Method: EM (single particle) / Resolution: 2.97 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • autographa californica nucleopolyhedrovirus
KeywordsSTRUCTURAL PROTEIN

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