Zaire ebolavirus glycoprotein GP1,2 (GP1,2)

The Zaire ebolavirus glycoprotein GP1,2 is a trimeric transmembrane protein that forms spikes on the virion surface and mediates viral entry into host cells. It is cleaved by furin-like proteases into GP1, the receptor-binding subunit responsible for attachment to unidentified host receptors, and GP2, the fusion subunit that drives membrane fusion via its internal fusion loop and heptad repeats. During entry, GP1,2 traffics to endosomes where cathepsins B and L proteolytically prime it by trimming GP1 to a 19-kDa form (residues 33-190), exposing a receptor-binding region (residues 90-149) critical for infection, while preserving GP2 integrity. The prefusion structure features GP1 forming a chalice-like bowl that clamps GP2's heptad repeat 1 (HR1) in a metastable conformation, preventing premature fusion; low pH and cleavage release this clamp, allowing GP2 to refold into a hairpin structure that apposes viral and host membranes. GP1,2 plays a central role in Zaire ebolavirus pathogenesis by enabling infection of permissive cells, with key conserved lysine residues (K95, K114, K115, K140) in primed GP1 essential for receptor engagement. Heavy glycosylation, including a mucin-like domain on GP1, forms a glycocalyx shield that evades humoral immunity. As a viral protein, GP1,2 is a prime therapeutic target for neutralizing antibodies and entry inhibitors, though no approved drugs directly target it as of current knowledge.

Other names

EBOV GPZEBOV GPEbola glycoproteinenvelope glycoprotein GP