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Evaluation of a Prefusion Model of the Herpesvirus Fusion Protein via Mutagenesis
Author(s) -
Robinson Carolyn A,
Gallagher Shan L,
Connolly Sarah A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.913.18
Subject(s) - biology , viral envelope , virology , lipid bilayer fusion , fusion protein , virus , sendai virus , glycoprotein , microbiology and biotechnology , computational biology , genetics , gene , recombinant dna
Herpesviruses affect a significant portion of the human population and cause a variety of diseases, including cold sores, chickenpox, mononucleosis, and some forms of cancer. The first step of any viral infection requires a virus to enter a host cell. Herpesviruses enter cells by fusing a lipid viral envelope with the host cell membrane. Glycoprotein B (gB), a virally‐encoded class III fusion protein, mediates this fusion event by physically inserting into the host cell membrane and refolding from a prefusion to a postfusion conformation. The crystal structure of gB in its postfusion form has been solved, but its prefusion structure is unknown. A model of the prefusion gB structure was created based on homology to another class III fusion protein. To assess this model, we introduced mutations into gB that we predicted would affect its fusion capacity by altering the stability of its prefusion conformation. Mutations were designed to increase the flexibility of a coiled‐coil that is extended in the postfusion structure but broken in the prefusion model. gB is an essential protein that is conserved in all herpesviruses. Insights into the molecular details of how the gB protein refolds to force membranes to fuse may identify targets for antiviral intervention. Support or Funding Information DePaul University Research Council Grant