title: Insertion of TAT peptide and perturbation of negatively charged model phospholipid bilayer revealed by neutron diffraction.
abstract: TAT peptide is one of the best-characterized cell penetrating peptides derived from the transactivator of transcription protein from the human immunodeficiency virus 1. The aim of this study was to investigate the interaction between TAT peptide and partially negatively-charged phospholipid bilayer by using lamellar neutron diffraction. The main findings are the existence of a contiguous water channel across the bilayer in the presence of TAT peptide. Taken in combination with other observations, including thinning of the lipid bilayer, this unambiguously locates the peptide within the lipid bilayer. The interaction of TAT peptide with anionic lipid bilayer, composed of an 80:20 mixture of DOPC and DOPS, takes place at two locations. One is in the peripheral aqueous phase between adjacent bilayers and the second is below the glycerol backbone region of bilayer. A membrane thinning above a peptide concentration threshold (1mol%) was found, as was a contiguous transbilayer water channel at the highest peptide concentration (10mol%). This evidence leads to the suggestion that the toroidal pore model might be involved in the transmembrane of TAT peptide. We interpret the surface peptide distribution in the peripheral aqueous phase to be a massive exclusion of TAT peptide from its intrinsic location below the glycerol backbone region of the bilayer, due to the electrostatic attraction between the negatively-charged headgroups of phospholipids and the positively charged TAT peptides. Finally, we propose that the role that negatively-charged headgroups of DOPS lipids play in the transmembrane of TAT peptide is less important than previously thought.
authors: Institute of Biotechnology, Fuzhou University, Fuzhou, Fujian, People's Republic of China.
authors: Xiaochao
authors: X
authors: Chen
authors: Farid
authors: F
authors: Sa'adedin
authors: Bruno
authors: B
authors: Deme
authors: Pingfan
authors: P
authors: Rao
authors: Jeremy
authors: J
authors: Bradshaw
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes; D056004:Molecular Dynamics Simulation; D033363:Neutron Diffraction; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism*; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015696:Gene Products, tat; D008051:Lipid Bilayers; D008081:Liposomes; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C042511:1,2-dioleoylphosphatidylserine; C017251:1,2-oleoylphosphatidylcholine