Structural basis for paramyxovirus-mediated membrane fusion

Paramyxoviruses are responsible for significant human mortality and disease worldwide, but the molecular mechanisms underlying their entry into host c ells remain poorly understood. We have solved the crystal structure of a fr agment of the simian parainfluenza virus 5 fusion protein (SV5 F), revealin g a 96 Angstrom long coiled coil surrounded by three antiparallel helices. This structure places the fusion and transmembrane anchor of SV5 F in close proximity with a large intervening domain at the opposite end of the coile d coil. Six amino acids, potentially part of the fusion peptide, form a seg ment of the central coiled coil, suggesting that this structure extends int o the membrane. Deletion mutants of SV5 F indicate that putative flexible t ethers between the coiled coil and the viral membrane are dispensable for f usion. The lack of flexible tethers may couple a final conformational chang e in the F protein directly to the fusion of two bilayers.