LL-37: How a tiny peptide carries out its great responsibility in the innate immune system

Authors

  • Nguyen Thi Huong Xuan International University- Vietnam National University
  • Tran Tong Khanh Linh
  • Phan Hoang Thien An
  • Nguyen Tan Khoi

DOI:

https://doi.org/10.15625/2615-9023/v40n2se.11576

Keywords:

LL-37, cathelicidin peptide, model cell membranes, peptide-membrane interaction.

Abstract

Elucidating the mode of action of antimicrobial peptides (AMPs) in cell membrane disruption is a topic of interest in understanding the efficiency of different AMPs, which is beneficial in designing antibiotics with desired potency and selectivity. As a key component of the innate immunity system, human cathelicidin LL-37 plays a crucial role in protecting human against infectious diseases. LL-37 kills cells by disrupting the membrane integrity through physical interaction with cell membranes. In this paper, we investigated the molecular interactions of LL-37 with various model cell membranes using Sum Frequency Generation (SFG), a modern vibrational spectroscopic technique. 1-palmitoyl-2-oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) supported bilayers were used as models for bacterial cell membranes and mammalian cell membranes, respectively. In our experiments, the helical
LL-37 molecules associated with the POPG/POPG bilayer surface at a tilt angle of 50o from the bilayer normal, indicating a toroidal pore mechanism of action for the peptide at a concentration of 400 nM. On the contrary, no interactions were observed between LL-37 and a zwitterionic POPC bilayer at much higher peptide concentrations (∼1.2 μM). Cholesterol is shown to suppress peptide-induced disorder in the lipid bilayer membranes.  These results would explain a selective effect of LL-37 on bacteria over mammalian cells. Additionally, in order to deduce the orientation of LL-37 on model cell membranes, we have introduced a modified data analysis approach. Our findings demonstrate that SFG is a powerful technique which can provide insights into the molecular interactions between antimicrobial peptides possessing multiple helical segments and cell membranes.

 

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Published

30-06-2018

How to Cite

Xuan, N. T. H., Linh, T. T. K., An, P. H. T., & Khoi, N. T. (2018). LL-37: How a tiny peptide carries out its great responsibility in the innate immune system. Academia Journal of Biology, 40(2se). https://doi.org/10.15625/2615-9023/v40n2se.11576

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