The solution structure and activity of caerin 1.1, an antimicrobial peptide from the Australian green tree frog, Litoria splendida.

Abstract

Caerin 1.1 is one of the major antimicrobial peptides isolated from the skin of the Australian green tree frog, Litoria splendida. Two-dimensional 1H-1H and 1H-13C NMR spectroscopy in trifluoroethanol/H2O (50:50, by vol.) have been used to assign the 1H and 13C-NMR spectra of this 25-amino-acid peptide. From an examination of these data, and using distance geometry and molecular dynamics calculations, the solution conformation of caerin 1.1 has been determined. The peptide adopts two well-defined helices from Leu2 to Lys11 and from Val17 to His24 separated by a region of less-defined helicity and greater flexibility. Overall, the peptide has a distinct amphipathic charge distribution. The solution structure of caerin 1.1 is compared with activity data against a variety of micro-organisms for the parent peptide and some naturally occurring and synthetic variants of caerin 1.1. The structural and activity data are consistent with caerin 1.1 interacting with membranes in a similar manner to other antimicrobial peptides, i.e. via a carpet-like mechanism whereby the individual peptides aggregate in a helical manner and orient themselves parallel to the membrane in a sheet-like arrangement [Shai, Y. (1995) Trends Biochem. Sci. 20, 460-464].