Ionic channels formed by a primary amphipathic peptide containing a signal peptide and a nuclear localization sequence.
The peptide SP-NLS (Ac-Met-Gly-Leu-Gly-Leu-His-Leu-Leu-Leu-Ala10-Ala-Ala-Leu-Gln-Gly- Ala -Lys-Lys-Lys-Arg20-Lys-Val-NH-CH2-CH2-SH) is composed of a hydrophobic signal sequence (SP, Met-1 to Ala-16) followed by a polycationic nuclear localization sequence (NLS, Lys-17 to Val-22) terminated by a cysteamide group. Designed to act as drug carrier this primary amphipathic peptide proved cytotoxic and bactericidal when used at high concentrations, probably by inducing the formation of ion channels. In this work, we show that indeed SP-NLS exhibits a pore-forming activity when incorporated into planar lipid bilayers and Xenopus laevis oocyte plasma membranes, with conductance values of 25 pS in 0.1 M NaCl. In both membranes, the insertion of the peptide was voltage-triggered whereas the induced conductances proved almost voltage-independent. Moreover, SP-NLS ion channels were selective for monovalent cations (K+>Na+>Li+>tetraethylammonium+>choline+). The ion channel activity of this type of peptides thus provides some insight on their toxicity but also on the mechanism involved for their membrane crossing process.
CRBM-CNRS, UPR 1086, 1919 Route de Mende, F-34293 Montpellier Cedex 5, France.
L
L
Chaloin
E
E
Dé
P
P
Charnet
G
G
Molle
F
F
Heitz
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D017421:Sequence Analysis; D014982:Xenopus laevis
D007473:Ion Channels; D010446:Peptide Fragments; D010455:Peptides