Conformational states of the cell-penetrating peptide penetratin when interacting with phospholipid vesicles: Effects of surface charge and peptide concentration

Mazin Magzoub, L. E.Göran Eriksson, Astrid Gräslund

Research output: Contribution to journalArticlepeer-review

Abstract

The most commonly studied of the cell-penetrating peptides (CPP) is "penetratin" (pAntp), which functions as a carrier (vector), even for large hydrophilic (cargo) molecules. pAntp originates from the third helix of the Antennapedia homeodomain protein. The peptide is known to interact with negatively charged phospholipid vesicles, which leads to induction of secondary structure. In the present study, circular dichroism (CD) spectroscopy has been used to characterize the different secondary structures induced upon interaction with small unilamellar vesicles (SUVs) from mixtures of zwitterionic 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG). The interaction was monitored using an electron paramagnetic resonance (EPR) spin probe attached to the peptide, and the intrinsic fluorophore (tryptophan). We measured the secondary structure as a function of surface charge density, total lipid-to-peptide (L/P) molar ratio, and salt concentration, for completely bound peptide. With vesicles from POPG/POPC in a molar ratio below 30:70, at a high L/P, the peptide adopts a mainly helical conformation. Increasing the charge density, at the same L/P, promotes a higher degree of β-structure. At a fixed charge density, reducing the L/P also results in an α→β structure conversion. Hence, low membrane surface charge density and low pAntp concentration both favor a mainly helical conformation, while high charge density and pAntp concentration promote a dominating β-structure. We conclude that pAntp, when residing at the surface of a membrane, is chameleon-like in terms of its induced structure.

Original languageEnglish (US)
Pages (from-to)53-63
Number of pages11
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1563
Issue number1-2
DOIs
StatePublished - Jun 13 2002

Keywords

  • Interaction
  • Penetratin
  • Phospholipid vesicle
  • Secondary structure
  • Surface charge

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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