Heptad-repeat regions of respiratory syncytial virus F-1 protein form a six-membered coiled-coil complex

The Respiratory Syncytial Virus (RSV) fusogenic glycoprotein Fl was charact erized using biochemical and biophysical techniques. Two heptad-repeat (HR) regions within Fl were shown to interact. Proteinase-K digestion experimen ts highlight the HR1 region (located proximal to the fusion peptide sequenc e) of the Fl protein to which an HR2-derived (located proximal to the membr ane-spanning domain) peptide binds, thus protecting both the protein and pe ptide from digestion. Solution-phase analysis of HR1-derived peptides shows that these peptides adopt helical secondary structure as measured by circu lar dichroism. Sedimentation equilibrium studies indicate that these HR1 pe ptides self-associate in a monomer/trimer equilibrium with an association c onstant of 5.2 x 10(8) M-2. In contrast, HR2-derived peptides form random m onomers in solution. CD analysis of mixtures containing peptides from the t wo regions demonstrate their propensity to interact and form a very stable (T-m = 87 degrees C), helical (86% helicity) complex comprised of three HR1 and three HR2 members.