Characterization of the structure-function relationship of a novel salt-resistant antimicrobial peptide, RR12

Abstract

Antimicrobial peptides (AMPs) are potential candidates in designing new anti-infective agents. However, many AMPs show poor bactericidal activities in physical salt and serum solutions. Here, we disclosed the structure-function relationships of a novel salt-resistant antimicrobial peptide, RR12, which could further explain its mode of action and show its applicability in developing new antibacterial agents.

Fig. 1. Far-UV CD spectra for RR12 in TFE, DPC and SDS micelles.

Fig. 2. NMR spectra and solution structure of RR12 in SDS micelles (PDB ID: 6J9P). (A) The ¹H–¹⁵N HSQC spectrum of RR12 in SDS micelles. (B) Superposition of the 20 lowest energy structures of RR12. The backbones and heavy chains are shown in blue lines. (C) Ribbon representation of the averaged SDS-bound solution structure. Arginine residues in blue are shown as balls and sticks. (D) The electrostatic surface of SDS-bound RR12.The positive charge is in blue, negative charge in red, and neutral positions in white.

Fig. 3. Calcein leakage caused by RR12 against the POPC and POPG LUVs.

Fig. 4. The position of RR12 in SDS micelles. (A) The remaining amplitudes of NH–C_αH cross peaks derived from the TOCSY spectra of RR12 due to 5- and 12-DSAs. The concentration of each DSA corresponds to a spin label per micelle. The magenta, cyan, and blue dotted lines indicate the mean remaining amplitudes of RR12 in the presence of 5-, 12-, and (0.5 mM) Mn²⁺ ions, individually. (B) The model structure of RR12 in complex with SDS micelle deduced from PRE results. The RR12 peptide was shown as magenta ribbon with arginine residues and R1, R2, R5, R9 and R12 presented in blue sticks. The SDS lipids were displayed as light-grey sticks with the sulphur atoms shown as spheres (yellow) and oxygen atoms were colored in red.

Fig. 5. Structural comparisons of RR12 with the known AMPs.