Molecular dynamics investigation of membrane-bound bundles of the channel-forming transmembrane domain of viral protein U from the human immunodeficiency virus HIV-1.
Molecular dynamics (MD) simulations have been carried out on bundles of the channel-forming transmembrane (TM) domain of the viral protein U (VPU(1-27) and VPU(6-27)) from the human immunodeficiency virus (HIV-1). Simulations of hexameric and pentameric bundles of VPU(6-27) in an octane/water membrane mimetic system suggested that the pentamer is the preferred oligomer. Accordingly, an unconstrained pentameric helix bundle of VPU(1-27) was then placed in a hydrated palmitoyl-oleyl-3-n-glycero-phosphatidylethanolamine (POPE) lipid bilayer and its structural properties calculated from a 3-ns MD run. Some water molecules, initially inside the channel lumen, were expelled halfway through the simulation and the bundle adopted a conical structure reminiscent of previous MD results obtained for VPU(6-27) in an octane/water system. The pore constriction generated may correspond to a closed state of the channel and underlies the relocation of the W residue toward the pore lumen. The relative positions of the helices with respect to the bilayer and their interactions with the lipids are discussed. The observed structure is stabilized via specific interactions between the VPU helices and the carbonyl oxygen atoms of the lipid molecules, particularly at the Q and S residues.
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323 USA.
Carlos F
CF
Lopez
Mauricio
M
Montal
J Kent
JK
Blasie
Michael L
ML
Klein
Preston B
PB
Moore
D002244:Carbon / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism*; D003198:Computer Simulation; D004583:Electrons; D015497:HIV-1 / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins; D008051:Lipid Bilayers / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009795:Octanes / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012984:Software; D013997:Time Factors; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D000086082:Viroporin Proteins
D002244:Carbon; D054298:Human Immunodeficiency Virus Proteins; D008051:Lipid Bilayers; D009795:Octanes; D010714:Phosphatidylethanolamines; D054334:Viral Regulatory and Accessory Proteins; D014867:Water; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; C026728:octane