Insertion of TAT peptide and perturbation of negatively charged model phospholipid bilayer revealed by neutron diffraction

Xiaochao Chen, Farid Sa'Adedin, Bruno Deme, Pingfan Rao, Jeremy Bradshaw

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 (1 mol%) was found, as was a contiguous transbilayer water channel at the highest peptide concentration (10 mol%). 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.

Original languageEnglish
Pages (from-to)1982-1988
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1828
Issue number8
Early online date1 May 2013
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Cell penetrating peptide
  • Neutron diffraction
  • Phospholipid
  • TAT peptide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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