Critical amino acid residues of maurocalcine involved in pharmacology, lipid interaction and cell penetration

Kamel Mabrouk, Narendra Ram, Sylvie Boisseau, Flavie Strappazzon, Amel Rehaim, Rémy Sadoul, Hervé Darbon, Michel Ronjat, Michel De Waard

Research output: Contribution to journalArticlepeer-review

Abstract

Maurocalcine (MCa) is a 33-amino acid residue peptide that was initially identified in the Tunisian scorpion Scorpio maurus palmatus. This peptide triggers interest for three main reasons. First, it helps unravelling the mechanistic basis of Ca2+ mobilization from the sarcoplasmic reticulum because of its sequence homology with a calcium channel domain involved in excitation-contraction coupling. Second, it shows potent pharmacological properties because of its ability to activate the ryanodine receptor. Finally, it is of technological value because of its ability to carry cell-impermeable compounds across the plasma membrane. Herein, we characterized the molecular determinants that underlie the pharmacological and cell-penetrating properties of maurocalcine. We identify several key amino acid residues of the peptide that will help the design of cell-penetrating analogues devoid of pharmacological activity and cell toxicity. Close examination of the determinants underlying cell penetration of maurocalcine reveals that basic amino acid residues are required for an interaction with negatively charged lipids of the plasma membrane. Maurocalcine analogues that penetrate better have also stronger interaction with negatively charged lipids. Conversely, less effective analogues present a diminished ability to interact with these lipids. These findings will also help the design of still more potent cell penetrating analogues of maurocalcine.

Original languageEnglish
Pages (from-to)2528-2540
Number of pages13
JournalBBA - Biomembranes
Volume1768
Issue number10
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Cell penetrating peptide
  • Cell penetration
  • Cell toxicity
  • Lipid interaction
  • Maurocalcine
  • Ryanodine receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Biophysics

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