title: HIV-1 Tat membrane interactions probed using X-ray and neutron scattering, CD spectroscopy and MD simulations.
abstract: We report the effect on lipid bilayers of the Tat peptide Y47GRKKRRQRRR57 from the HIV-1 virus transactivator of translation (Tat) protein. Synergistic use of low-angle X-ray scattering (LAXS) and atomistic molecular dynamic simulations (MD) indicate Tat peptide binding to neutral dioleoylphosphocholine (DOPC) lipid headgroups. This binding induced the local lipid phosphate groups to move 3Å closer to the center of the bilayer. Many of the positively charged guanidinium components of the arginines were as close to the center of the bilayer as the locally thinned lipid phosphate groups. LAXS data for DOPC, DOPC/dioleoylphosphoethanolamine (DOPE), DOPC/dioleoylphosphoserine (DOPS), and a mimic of the nuclear membrane gave similar results. Generally, the Tat peptide decreased the bilayer bending modulus KC and increased the area/lipid. Further indications that Tat softens a membrane, thereby facilitating translocation, were provided by wide-angle X-ray scattering (WAXS) and neutron scattering. CD spectroscopy was also applied to further characterize Tat/membrane interactions. Although a mechanism for translation remains obscure, this study suggests that the peptide/lipid interaction makes the Tat peptide poised to translocate from the headgroup region.
authors.affiliation: Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, United States.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Akabori
authors.affiliation: Department of Physics, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, United States.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, United States.
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Treece
authors.affiliation: Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Jablin
authors.affiliation: NIST Center for Neutron Research, 100 Bureau Drive, Stop 6102, Gaithersburg, MD 20899, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Maranville
authors.affiliation: CHESS, Cornell University, 161 Synchrotron Drive, Ithaca, NY 14853, United States.
authors.forename: Arthur
authors.initials: A
authors.lastname: Woll
authors.affiliation: Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Nagle
authors.affiliation: Department of Physics, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, NY 12180, United States.
authors.forename: Angel E
authors.initials: AE
authors.lastname: Garcia
authors.affiliation: Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA, United States. Electronic address: stn@cmu.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tristram-Nagle
keywords: Lipid bilayer structure cell-penetrating peptide; Low-angle X-ray scattering (LAXS); Membrane pore; Molecular dynamics (MD) simulations; Peptide translocation; Wide-angle X-ray scattering (WAXS)