Lipophosphoglycan of Leishmania donovani inhibits lipid vesicle fusion induced by the N-terminal extremity of viral fusogenic simian immunodeficiency virus protein.
Lipophosphoglycan (LPG), the major glycoconjugate of Leishmania parasites, was recently shown to be a potent inhibitor of viral infection. The mechanism by which this natural membrane amphiphile compound inhibits membrane fusion was investigated in this study using a simple model membrane system and a synthetic peptide corresponding to the fusion peptide of simian immunodeficiency virus (SIV). At low concentration (< 10 microM), LPG inhibits SIV-induced lipid mixing of large unilamellar vesicles composed of an equimolar mixture of egg phosphatidylcholine and egg phosphatidylethanolamine. Importantly, this inhibition was observed regardless of which LPG was inserted in the inner monolayer, the outer monolayer or both sides of the membrane, suggesting that the inner monolayer plays a determining role in membrane fusion. Fourier transform infrared spectroscopy revealed that LPG induced a conformational change of SIV fusion peptide without affecting its capacity to interact with the lipid membrane. This structural change was shown not to depend on the LPG localization and was observed even when LPG was exclusively associated to the inner lipid membrane.
Martin
I
I
Laboratoire de Chimie-Physique des Macromolécules aux Interfaces (LCPMI) CP206/2, Université Libre de Bruxelles, Brussels, Belgium. imartin@ulb.ac.be
Turco
S J
SJ
Epand
R M
RM
Ruysschaert
J M
JM
D000818:Animals; D002240:Carbohydrate Sequence; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism*; D007893:Leishmania donovani / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
D006028:Glycosphingolipids; D010446:Peptide Fragments; D014764:Viral Proteins; C008290:lipophosphonoglycan