Summary
Prefusion stabilization of viral fusion proteins often requires combinations of mutations, but single substitutions can suffice in some proteins. The S-2P and HexaPro SARS-CoV-2 spike designs use two and six proline substitutions, respectively (1). In contrast, P22L alone stabilized the PIV5 fusion protein in its prefusion state, and the homologous G34L substitution stabilized Newcastle disease virus F (2).
1.
Hsieh C-L, Goldsmith JA, Schaub JM, DiVenere AM, Kuo H-C, Javanmardi K, et al. Structure-based design of prefusion-stabilized SARS-CoV-2 spikes. Science. 2020;369(6510):1501–5. Available from: https://doi.org/10.1126/science.abd0826
2.
Song AS, Poor TA, Abriata LA, Jardetzky TS, Dal Peraro M, Lamb RA. Immobilization of the N-terminal helix stabilizes prefusion paramyxovirus fusion proteins. Proceedings of the National Academy of Sciences. 2016;113(27):E3844–51. Available from: https://doi.org/10.1073/pnas.1608349113