title: Critical amino acid residues of maurocalcine involved in pharmacology, lipid interaction and cell penetration.
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 Ca(2+) 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.
authors: Laboratoire Chimie Biologie et Radicaux Libre, Universite Aix-Marseille, Avenue Escadrille Normandie Niemen, 13397 Marseille, France.
authors: Kamel
authors: K
authors: Mabrouk
authors: Narendra
authors: N
authors: Ram
authors: Sylvie
authors: S
authors: Boisseau
authors: Flavie
authors: F
authors: Strappazzon
authors: Amel
authors: A
authors: Rehaim
authors: Rémy
authors: R
authors: Sadoul
authors: Hervé
authors: H
authors: Darbon
authors: Michel
authors: M
authors: Ronjat
authors: Michel
authors: M
authors: De Waard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D008563:Membrane Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D012433:Ryanodine / Q000378:metabolism; D012604:Scorpion Venoms / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008563:Membrane Lipids; D012604:Scorpion Venoms; C406406:maurocalcine; D012433:Ryanodine