Poster Presentation The 45th Lorne Conference on Protein Structure and Function 2020

Structural and functional characterization of insect defensins (#325)

Zhanzhao Yang 1 , Marc Prof. Kvansakul 1 , Mark Prof. Hulett 1
  1. La Trobe University, Bundoora, VICTORIA, Australia

Defensins are a huge category of cationic antimicrobial peptides in the innate immune system which can be found in most species including plants, insects, reptiles and mammals1. These molecules harbor a wide antimicrobial spectrum against many pathogens such as bacteria, fungi, viruses and even parasites2-4. As there are more and more reports of pathogenic microbes showing resistance to conventional antibiotics, defensins have drawn a lot of attention as novel therapeutics against drug-resistant microbes due to their distinct mechanism5. Different techniques have been applied to study the mechanism of defensins’ antimicrobial peptides, but the actual mode of action is still under debate. Currently popular models such as Shai-Matsuzaki-Huang model explain that defensins may work as pore formers on cell membranes by interacting with lipids. Therefore, it is important to determine the structure of pore-formed defensins with lipids6. Previous studies demonstrated that human and plant
defensins can form pores and insert into cell membranes with various experiments such as lipid overlay assays, chemical crosslinking assays and structure determination through X-ray crystallography7,8. However, insect defensins’ mechanism is not clear yet. Our research shows that drosomycins from Drosophila melanogaster, Apis cerana defensin 1 and coprisins from Copris tripartitus have the lipid-binding ability as well. And various assays indicate their similar mode of actions to defensins in plants and humans.

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  8. Jarva M, Phan TK, Lay FT, Caria S, Kvansakul M, Hulett MD (2018) "Human beta-defensin 2 kills Candida albicans through phosphatidylinositol 4,5-bisphosphate-mediated membrane permeabilization", Science advances, 4: eaat0979