The structure of a prokaryotic viral envelope protein expands the landscape of membrane fusion proteins

Kamel El Omari, Sai Li, Abhay Kotecha, Thomas S. Walter, Eduardo A. Bignon, Karl Harlos, Pentti Somerharju, Felix Haas, Daniel K. Clare, Mika Molin, Felipe Hurtado, Mengqiu Li, Jonathan M. Grimes, Dennis H. Bamford, Nicole D. Tischler (), Juha T. Huiskonen (), David I. Stuart () and Elina Roine ()
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Kamel El Omari: University of Oxford
Sai Li: University of Oxford
Abhay Kotecha: University of Oxford
Thomas S. Walter: University of Oxford
Eduardo A. Bignon: Laboratorio de Virología Molecular
Karl Harlos: University of Oxford
Pentti Somerharju: University of Helsinki
Felix Haas: Thermo Fisher Scientific
Daniel K. Clare: Diamond Light Source Limited, Harwell Science and Innovation Campus
Mika Molin: Institute of Biotechnology, University of Helsinki
Felipe Hurtado: Laboratorio de Virología Molecular
Mengqiu Li: University of Oxford
Jonathan M. Grimes: University of Oxford
Dennis H. Bamford: University of Helsinki
Nicole D. Tischler: Laboratorio de Virología Molecular
Juha T. Huiskonen: University of Oxford
David I. Stuart: University of Oxford
Elina Roine: University of Helsinki

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Lipid membrane fusion is an essential function in many biological processes. Detailed mechanisms of membrane fusion and the protein structures involved have been mainly studied in eukaryotic systems, whereas very little is known about membrane fusion in prokaryotes. Haloarchaeal pleomorphic viruses (HRPVs) have a membrane envelope decorated with spikes that are presumed to be responsible for host attachment and membrane fusion. Here we determine atomic structures of the ectodomains of the 57-kDa spike protein VP5 from two related HRPVs revealing a previously unreported V-shaped fold. By Volta phase plate cryo-electron tomography we show that VP5 is monomeric on the viral surface, and we establish the orientation of the molecules with respect to the viral membrane. We also show that the viral membrane fuses with the host cytoplasmic membrane in a process mediated by VP5. This sheds light on protein structures involved in prokaryotic membrane fusion.

Date: 2019
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DOI: 10.1038/s41467-019-08728-7

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