The role of membranes in the organization of HIV-1 Gag p6 and Vpr: p6 shows high affinity for membrane bilayers which substantially increases the interaction between p6 and Vpr.
The molecular mechanism by which HIV-1 Gag proteins are targeted and transported to the plasma membrane after ribosomal synthesis is unknown. In this work, we investigated the potential interaction of p6 and Vpr with model membranes and have determined their binding constants. Plasmon waveguide resonance (PWR) experiments showed that p6 strongly interacts with membranes (K(d) approximately 40 nM), which may help explaining in part why Gag is targeted to and assembles into membranes by coating itself with lipids. Moreover, a substantial increased affinity of Vpr for p6 was observed while in a membrane environment. In order to further investigate the molecular properties behind the high affinity to model membranes, molecular dynamics simulations were carried out for p6 with a dodecylphosphocholine (DPC) micelle. The results indicate an integration route model for Vpr into virions and may help explain why previous reports failed to detect p6 in virion core preparations.
Salgado
Gilmar F
GF
Departement de Chimie, Ecole Normale Superieure, CNRS, UMR 8642, 24 rue Lhomond, 75231 Paris cedex 05, France.
Vogel
Alexander
A
Marquant
Rodrigue
R
Feller
Scott E
SE
Bouaziz
Serge
S
Alves
Isabel D
ID
D000595:Amino Acid Sequence; D002152:Calorimetry, Differential Scanning; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D016336:Gene Products, vpr / Q000378:metabolism*; D015497:HIV-1; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008823:Micelles; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010063:Ovum; D044367:Phase Transition; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism*
D016336:Gene Products, vpr; D008051:Lipid Bilayers; D008823:Micelles; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; D004134:Dimyristoylphosphatidylcholine