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].

Antimicrobial peptides from amphibian skin: What do they tell us?

“…78,80,81 For the 25-residue peptide caerin 1.1, the solution conformation has been determined using distance geometry and molecular dynamics calculations. 82 The structural and activity data suggest an interaction with membranes via a carpet-like mechanism. 24 Two other families of antimicrobial peptides have been isolated from L. infrafrenata and L. genimaculata, and were termed frenatins and maculatins, respectively.…”

Animal antimicrobial peptides: An overview

“…A number of secondary structures of antimicrobial peptides, broadly representative of the above structural groups, have been determined by two-dimensional nmr, either in solution or in model membrane environments. They include cecropins, 89 -92 magainins, [93][94][95] PGLa, 96 sarcotoxin, 97 buforin, 98 caerin, 99 bactenecins, 100 enkelytin, 101 histatin, 102 ranalexin, 103 thanatin, 104 protegrin, 105 tachyplesin, 106 different types of defensins, [107][108][109][110][111][112][113][114][115] and drosomycin.…”

Histidine‐containing host‐defence skin peptides of anurans bind Cu2+. An electrospray ionisation mass spectrometry and computational modelling study

“…The "helix-hinge-helix" structure of caerin 1.1 (GLLSVLGSVAKHVLPHVVPVIAEHL-NH 2 ), determined by 2D NMR in aqueous d 3 -trifluoroethanol as solvent. [3,4] T. Wang et al 03 suite of program [39] at the HF/6-31G* + 5D level of theory by using an iterative least-squares method, see Supporting Information). The restrained electrostatic potential (RESP) charge method developed by Kollman [40] was used for atomic charges, which were then fitted using the RED program.…”

“…[1,2] Nuclear magnetic resonance (NMR) studies show that the caerins 1 are hinged peptides when attached to a membrane bilayer. [3,4] Figure 1 shows the three-dimensional (3D) structure of the helix-hinge-helix amphipathic peptide caerin 1.1 and it is suggested that caerin 1.1 interacts with the lipid bilayer of bacterial cells as shown in Fig. 2, [1,2] with the central hinge allowing for insertion of the terminal helix into the membrane, disrupting membrane integrity.…”