title: Heptad-repeat regions of respiratory syncytial virus F1 protein form a six-membered coiled-coil complex.
abstract: The Respiratory Syncytial Virus (RSV) fusogenic glycoprotein F(1) was characterized using biochemical and biophysical techniques. Two heptad-repeat (HR) regions within F(1) were shown to interact. Proteinase-K digestion experiments highlight the HR1 region (located proximal to the fusion peptide sequence) of the F(1) protein to which an HR2-derived (located proximal to the membrane-spanning domain) peptide binds, thus protecting both the protein and peptide from digestion. Solution-phase analysis of HR1-derived peptides shows that these peptides adopt helical secondary structure as measured by circular dichroism. Sedimentation equilibrium studies indicate that these HR1 peptides self-associate in a monomer/trimer equilibrium with an association constant of 5.2 x 10(8) M(-2). In contrast, HR2-derived peptides form random monomers in solution. CD analysis of mixtures containing peptides from the two 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.
authors.affiliation: Trimeris, Inc., 4727 University Drive, Durham, North Carolina 27707, USA. mdelmedico@trimeris.com
authors.forename: M K
authors.initials: MK
authors.lastname: Lawless-Delmedico
authors.forename: P
authors.initials: P
authors.lastname: Sista
authors.forename: R
authors.initials: R
authors.lastname: Sen
authors.forename: N C
authors.initials: NC
authors.lastname: Moore
authors.forename: J B
authors.initials: JB
authors.lastname: Antczak
authors.forename: J M
authors.initials: JM
authors.lastname: White
authors.forename: R J
authors.initials: RJ
authors.lastname: Greene
authors.forename: K C
authors.initials: KC
authors.lastname: Leanza
authors.forename: T J
authors.initials: TJ
authors.lastname: Matthews
authors.forename: D M
authors.initials: DM
authors.lastname: Lambert
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D019286:Endopeptidase K; D015707:HN Protein; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D018113:Respiratory Syncytial Virus, Human / Q000737:chemistry* / Q000235:genetics; D014461:Ultracentrifugation; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D015707:HN Protein; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C116204:attachment protein G; D019286:Endopeptidase K