Chapter Category: Viruses

From the book Viral Entry into Host Cells

Class II Fusion Proteins

Yorgo Modis

Enveloped viruses rely on fusion proteins in their envelope to fuse the viral membrane to the host‑cell membrane. This key step in viral entry delivers the viral genome into the cytoplasm for replication. Although class II fusion proteins are genetically and structurally unrelated to class I fusion proteins, they use the same physical principles and topology as other fusion proteins to drive membrane fusion. Exposure of a fusion loop first allows it to insert into the host‑cell membrane. Conserved hydrophobic residues in the fusion loop act as an anchor, which penetrates only partway into the outer bilayer leaflet of the host‑cell membrane. Subsequent folding back of the fusion protein on itself directs the C‑terminal viral transmembrane anchor towards the fusion loop. This fold‑back forces the host‑cell membrane (held by the fusion loop) and the viral membrane (held by the C‑terminal transmembrane anchor) against each other, resulting in membrane fusion. In class II fusion proteins, the fold‑back is triggered by the reduced pH of an endosome, and is accompanied by the assembly of fusion protein monomers into trimers. The fold‑back occurs by domain rearrangement rather than by an extensive refolding of secondary structure, but this domain rearrangement and the assembly of monomers into trimers together bury a large surface area. The energy that is thus released exerts a bending force on the apposed viral and cellular membranes, causing them to bend towards each other and, eventually, to fuse.


Taken from the book

Viral Entry into Host Cells

Edited by: Stefan Pöhlmann and Graham Simmons

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