Lipid-specific protein oligomerization is regulated by two interfaces in Marburg virus matrix protein VP40

Amiar, S.; Husby, M. L.; Wijesinghe, K. J.; Angel, S.; Bhattarai, N.; Gerstman, B. S.; Chapagain, P. P.; Li, S.; Stahelin, R. V.

doi:10.1101/2020.11.13.381350

bioRxiv · 10.1101/2020.11.13.381350

Lipid-specific protein oligomerization is regulated by two interfaces in Marburg virus matrix protein VP40

Amiar, S.·Husby, M. L.·Wijesinghe, K. J.·Angel, S.·Bhattarai, N.·Gerstman, B. S.·Chapagain, P. P.·Li, S.·Stahelin, R. V.

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Abstract

Marburg virus major matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane and undergo a dynamic and extensive self-oligomerization into the structural matrix layer which confers the virion shape and stability. Using a myriad of in vitro and cellular techniques, we present a mVP40 assembly model highlighting two distinct oligomerization interfaces (N-terminal domain (NTD) and C-terminal domain (CTD)) in mVP40. Cellular studies of NTD and CTD oligomerization interface mutants demonstrated the importance of each interface in the mVP40 matrix assembly through protein trafficking to the plasma membrane and homo-multimerization that induced protein enrichment, plasma membrane fluidity changes and elongations at the plasma membrane. A novel APEX-TEM method was employed to closely assess the ultrastructural localization of and formation of viral particles for wild type and mutants. Taken together, these studies present a mechanistic model of mVP40 oligomerization and assembly at the plasma membrane during virion assembly.

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Amiar, S., Husby, M. L., Wijesinghe, K. J., Angel, S., Bhattarai, N., Gerstman, B. S., Chapagain, P. P., Li, S., Stahelin, R. V.. 2020-11-14. Lipid-specific protein oligomerization is regulated by two interfaces in Marburg virus matrix protein VP40. https://doi.org/10.1101/2020.11.13.381350

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