Structure-Based Mutations in the Herpes Simplex Virus 1 Glycoprotein B Ectodomain Arm Impart a Slow-Entry Phenotype

Fan, Qing; Kopp, Sarah J.; Connolly, Sarah A.; Longnecker, Richard

The gB 3A mutations were designed to reduce interactions between the domain V arm and the helical central coiled coil of gB (20) , on the basis of the postfusion structure of HSV-1 gB (12) (Fig. 1A) . Because of the similarity of the gB coil-arm complex to the six-helix bundle of class I fusion proteins, we hypothesized that the gB coil-arm interactions are important for the transition from a prefusion to a postfusion conformation and that gB 3A mutations would alter the energetics of gB refolding (Fig. 10) . The slow-entry phenotype of the gB 3A viruses and the ability of heat to rescue their cell penetration support our hypothesis that interaction between the arm and coil regions of gB is an important step in the refolding of gB (20) .