Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-angstrom resolution

Ebola virions contain a surface transmembrane glycoprotein (GP) that is res ponsible for binding to target cells and subsequent fusion of the viral and host-cell membranes. GP is expressed as a single-chain precursor that is p osttranslationally; processed into the disulfide-linked fragments GPI and G P2. The GP2 subunit is thought to mediate membrane fusion, A soluble fragme nt of the GP2 ectodomain, lacking the fusion-peptide region and the transme mbrane helix, folds into a stable, highly helical structure in aqueous solu tion. Limited proteolysis studies identify a stable core of the GP2 ectodom ain, This 74-residue core, denoted Ebo-74, was crystallized, and its x-ray structure was determined at 1.9-Angstrom resolution. Ebo-74 forms a trimer in which a long, central three-stranded coiled coil is surrounded by shorte r C-terminal helices that are parked in an antiparallel orientation into hy drophobic grooves on the surface of the coiled coil, Our results confirm th e previously anticipated structural similarity between the Ebola GP2 ectodo main and the core of the transmembrane subunit from oncogenic retroviruses. The Ebo-74 structure likely represents the fusion-active conformation of t he protein, and its overall architecture resembles several other viral memb rane-fusion proteins, including those from HIV and influenza.