Heptad-repeat regions of respiratory syncytial virus F1 protein form a six-membered coiled-coil complex.
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.
Lawless-Delmedico
M K
MK
Trimeris, Inc., 4727 University Drive, Durham, North Carolina 27707, USA. mdelmedico@trimeris.com
Sista
P
P
Sen
R
R
Moore
N C
NC
Antczak
J B
JB
White
J M
JM
Greene
R J
RJ
Leanza
K C
KC
Matthews
T J
TJ
Lambert
D M
DM
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
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