Hj. Kim et al., Gaegurin 4, a peptide antibiotic of frog skin, forms voltage-dependent channels in planar lipid bilayers, J PEPT RES, 53(1), 1999, pp. 1-7
Gaegurin 4 (GGN4) is a cationic peptide of 37 amino acids (MW 3748) isolate
d from the skin of Rana rugosa. It has shown a broad spectrum antimicrobial
activity in vitro against Gram-negative and -positive bacteria, fungi and
protozoa. To understand its mechanism of antimicrobial action, we examined
the effect of GGN4 on the membrane conductance and the electrical propertie
s of GGN4-induced pores in planar lipid bilayers under voltage clamp. Natur
al and synthetic GGN4 (0.01-1 mu g/mL) increased the membrane conductance i
n a concentration-dependent manner, but GGN4 (1-23), an N-terminal fragment
of the peptide with little antimicrobial activity, failed to increase the
conductance. At symmetrical 100 mM KCl, unitary conductances of about 120 p
S were frequently observed. Their current-voltage relations were linear and
open state probabilities were close to 1, but longer closing events were s
een more frequently at negative voltages. In addition, GGN4-induced pores w
ere selective for cation over anion, the permeability ratio of K+ to Cl- be
ing 6.1 in neutral and 7:1 in acidic lipid bilayers. In conclusion, our res
ults indicate that GGN4 forms voltage-dependent and cation-selective pores
in planar lipid bilayers. The ionophoric property of GGN4 is likely to cont
ribute to its antimicrobial activity.