Key result
Stability complementation between the N465H substitution and DIII domain mutations conferred efficient cell-cell fusion activity on the measles virus F protein at 37 °C.
Intramolecular complementation between stabilizing and destabilizing mutations in the measles virus F protein restores optimal cell-cell fusion activity at physiological temperature.
May inform measles antiviral design; leaves open in vivo relevance and human translation.
The fusion (F) protein of measles virus mediates membrane fusion. In this study, we investigated the molecular basis of the cell-cell fusion activity of the F protein. The N465H substitution in the heptad repeat B domain of the stalk region of the F protein eliminates this activity, but an additional mutation in the DIII domain of the head region - N183D, F217L, P219S, I225T or G240R - restores cell-cell fusion. Thermodynamically stabilized by the N465H substitution, the F protein required elevated temperature as high as 40 °C to promote cell-cell fusion, whereas all five DIII mutations caused destabilization of the F protein allowing the highest fusion activity at 30 °C. Stability complementation between the two domains conferred an efficient cell-cell fusion activity on the F protein at 37 °C.
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Satoh et al. (2014) studied this question. N465H substitution and DIII domain mutations was evaluated on Cell-cell fusion activity. Stability complementation between the N465H substitution and DIII domain mutations conferred efficient cell-cell fusion activity on the measles virus F protein at 37 °C.
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