Phospholipid interactions of a peptide from the fusion-related domain of the glycoprotein of VHSV, a fish rhabdovirus.
Previous studies mapped a p2 domain (aa 82-109) which binds phosphatidylserine (PS) (Estepa and Coll, 1996a) and contains three contiguous hydrophobic amino acid heptad repeats followed by a positively charged stretch (Coll, 1995b) in the glycoprotein G of the viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus. Anti-p2 antibodies inhibited low-pH VHSV-induced fusion (Estepa and Coll, 1997) and low-pH PS binding to VHSV (Estepa and Coll, 1996a). We report here further studies on the interaction of the synthetic peptide p2 with phospholipid vesicles. The synthetic p2 peptide was able to mediate aggregation, lipid mixing, and leakage of contents only with negatively charged phospholipid vesicles and in a concentration-dependent manner. As shown by its effect on lipid phase transitions deduced from data with fluorescence polarization and differential scanning calorimetry, the p2 peptide becomes inserted into the hydrophobic negatively charged phospholipid vesicle bilayers. In addition, data based on circular dichroism showed that the p2 peptide folds as a structure with a high content of beta-sheets stabilized by interaction with anionic phospholipids. These studies are potentially relevant to viral fusion in VHSV.
Nuñez
E
E
Departamento de Bioquímica y Biología Molecular, Ciencias Químicas, Universidad Complutense, Madrid, Spain.
Fernandez
A M
AM
Estepa
A
A
Gonzalez-Ros
J M
JM
Gavilanes
F
F
Coll
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D005399:Fishes / Q000821:virology; D008051:Lipid Bilayers; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D011487:Protein Conformation; D012209:Rhabdoviridae / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
C096089:G protein, viral hemorrhagic septicemia virus; D008051:Lipid Bilayers; D008562:Membrane Glycoproteins; D010455:Peptides; D010743:Phospholipids; D014759:Viral Envelope Proteins