Chiroptical Properties and Conformation of Four Lasiocepsin-Related Antimicrobial Peptides: Structural Role of Disulfide Bridges

Markéta Pazderková,Lucie Bednárová,Václav Čeřovský,Petr Maloň,Vladimír Baumruk,Václav Profant,Rina K Dukor

doi:10.3390/sym12050812

Abstract

We report an investigation of the role of disulfide bridges in the 27-residue antimicrobial peptide lasiocepsin (I) containing two disulfide groups (Cys8–Cys25, Cys17–Cys27) and three its analogs lacking one (II, III) or both (IV) native disulfides. Selective alternate incorporation of one or both disulfide bridges influences symmetry, conformation and biological properties of these peptides as demonstrated in their chiroptical (particularly Raman) properties. The effect of modifying the disulfide bridge pattern on the peptide secondary structure is investigated in water and in the presence of 2,2,2-trifluoroethanol and sodium dodecyl sulphate. A combination of experimental electronic and vibrational chiroptical data shows that both disulfide groups are necessary for stabilizing lasiocepsin secondary structure. While the Cys8–Cys25 disulfide group is important for sustaining lasiocepsin tertiary structure and maintaining its biological activity, the Cys17–Cys27 disulfide bridge has a supporting function consisting in reducing peptide flexibility.

Highlights

Lasiocepsin (I, see Figure 1, Table 1), a 27-residue peptide exhibiting substantial antibacterial and antifungal activities, has been discovered in the venom of eusocial bee Lasioglossum laticeps [1]
We have shown that a combination of optical and chiroptical spectroscopic techniques represents an effective tool for inspecting lasiocepsin conformation in different environments and that the set of these techniques can be potentially used for studying mechanism of antimicrobial peptides (AMPs) action
For the natural peptide I both in aqueous and in sodium dodecylsulfate (SDS) micelle-containing solution, secondary structure estimation derived from chiroptical data correlates well with the published NMR structure [20]

Summary

Introduction

Lasiocepsin (I, see Figure 1, Table 1), a 27-residue peptide exhibiting substantial antibacterial and antifungal activities, has been discovered in the venom of eusocial bee Lasioglossum laticeps [1]. AMPs are in focus of scientific interest, because, compared to common antibiotics, they are less specific and evolution of bacterial resistance is typically rather limited [7] These circumstances bring potential for the development of novel drugs and, AMPs are the subject of intense investigation concerning their structures, activities and mechanisms of action [3,4,8,9,10,11,12,13,14,15]. Antimicrobial action involves interaction of sides of these α-helical segments with

Methods

Results

Discussion

Conclusion