title: HIV-1 matrix-31 membrane binding peptide interacts differently with membranes containing PS vs. PI(4,5)P2.
abstract: Efficient assembly of HIV-1 at the plasma membrane (PM) of the T-cell specifically requires PI(4,5)P2. It was previously shown that a highly basic region (HBR) of the matrix protein (MA) on the Gag precursor polyprotein Pr55Gagis required for membrane association. MA is N-terminally myristoylated, which enhances its affinity to membranes. In this work we used X-ray scattering and neutron reflectivity to determine how the physical properties and structure of lipid bilayers respond to the addition of binding domain peptides, either in the myristoylated form (MA31myr) or without the myristoyl group (MA31). Neutron reflectivity measurements showed the peptides predominantly located in the hydrocarbon interior. Diffuse X-ray scattering showed differences in membrane properties upon addition of peptides and the direction of the changes depended on lipid composition. The PI(4,5)P2-containing bilayers softened, thinned and became less ordered as peptide concentration increased. In contrast, POPS-containing bilayers with equivalent net charge first stiffened, thickened and became more ordered with increasing peptide concentration. As softening the host cell's PM upon contact with the protein lowers the free energy for membrane restructuring, thereby potentially facilitating budding of viral particles, our results suggest that the role of PI(4,5)P2in viral assembly goes beyond specific stereochemical membrane binding. These studies reinforce the importance of lipids in virology.
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: O'Neil
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Andenoro
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Isabella
authors.initials: I
authors.lastname: Pagano
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Carroll
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Leah
authors.initials: L
authors.lastname: Langer
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Dell
authors.affiliation: Biomedical Engineering, Douglass College, Rutgers University, New Brunswick, NJ 08901, United States.
authors.forename: Davina
authors.initials: D
authors.lastname: Perera
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Bradley W
authors.initials: BW
authors.lastname: Treece
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States; National Institute of Standards and Technology Center for Neutron Research, Gaithersburg, MD 20899, United States.
authors.forename: Frank
authors.initials: F
authors.lastname: Heinrich
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States; National Institute of Standards and Technology Center for Neutron Research, Gaithersburg, MD 20899, United States; Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: Mathias
authors.initials: M
authors.lastname: Lösche
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Nagle
authors.affiliation: Biological Physics Group, Physics Department, Carnegie Mellon University, Pittsburgh, PA 15213, United States. Electronic address: stn@cmu.edu.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Tristram-Nagle
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated; D015497:HIV-1 / Q000502:physiology*; D008051:Lipid Bilayers / Q000737:chemistry; D009502:Neutrons; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry*; D012542:Scattering, Radiation; D014763:Viral Matrix Proteins; D019065:Virus Assembly; D014965:X-Rays; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry*
chemical_list: D005229:Fatty Acids, Monounsaturated; D008051:Lipid Bilayers; D019269:Phosphatidylinositol 4,5-Diphosphate; D010718:Phosphatidylserines; D014763:Viral Matrix Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054211:9-tetradecenoic acid
keywords: Area/lipid; Bending modulus; Bilayer thickness; Neutron reflectivity; S(xray) order parameter; X-ray diffuse scattering