Schistocins: novel antimicrobial peptides encrypted in the Schistosoma mansoni Kunitz Inhibitor SmKI-1
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2021
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Background: Here we describe a new class of cryptides (peptides encrypted within a larger protein) with antimicrobial properties, named schistocins, derived from SmKI-1, a key protein in Shistosoma mansoni survival. This
is a multi-functional protein with biotechnological potential usage as a therapeutic molecule in inflammatory
diseases and to control schistosomiasis.
Methods: We used our algorithm enCrypted, to perform an in silico proteolysis of SmKI-1 and a screening for
potential antimicrobial activity. The selected peptides were chemically synthesized, tested in vitro and evaluated
by both structural (CD, NMR) and biophysical (ITC) studies to access their structure-function relationship.
Results: EnCrypted was capable of predicting AMPs in SmKI-1. Our biophysical analyses described a membraneinduced conformational change from random coil-to-α-helix and a peptide-membrane equilibrium for all
schistocins. Our structural data allowed us to suggest a well-known mode of peptide-membrane interaction in
which electrostatic attraction between the cationic peptides and anionic membranes results in the bilayer disordering. Moreover, the NMR H/D exchange data with the higher entropic contribution observed for the peptidemembrane interaction showed that schistocins have different orientations upon the membrane.
Conclusions: This work demonstrate the robustness for using the physicochemical features of predicted peptides
in the identification of new bioactive cryptides. Besides, it demonstrates the relevance of combining these analyses with biophysical methods to understand the peptide-membrane affinity and improve further algorithms.
General significance: Bioprospecting cryptides can be conducted through data mining of protein databases
demonstrating the success of our strategy. The peptides-based agents derived from SmKI-1 might have high
impact for system-biology and biotechnology.
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Cryptides, Peptide conformation, Peptide design, Nuclear magnetic resonance (NMR)
Citação
SANTOS, B. P. O. et al. Schistocins: novel antimicrobial peptides encrypted in the Schistosoma mansoni Kunitz Inhibitor SmKI-1. Biochimica et Biophysica Acta (BBA): general subjects, Amsterdam, v. 1865, e129989, 2021. DOI: 10.1016/j.bbagen.2021.129989. Disponível em: https://www.sciencedirect.com/science/article/pii/S0304416521001483?via%3Dihub. Acesso em: 16 fev. 2024.