6n68 | pdb_00006n68
NMR solution structure of Protonectin (Agelaia pallipes pallipes) interacting with SDS micelles: an antimicrobial peptide with anticancer activity on breast cancer cells
Structural highlights
Function[PROTO_AGEPP] Shows potent antimicrobial action against both Gram-positive and Gram-negative bacteria (MIC=25 ug/ml or 32-63 uM against E.coli, MIC=1.7 ug/ml against P.aeruginosa, MIC=3.1 ug/ml or 4 uM against B.subtilis, MIC=8 uM against S.epidermis, and MIC=12.5 ug/ml or 8 uM against S.aureus) (PubMed:15225564, PubMed:23836163). Acts by disrupting the integrity of the outer and inner bacterial membranes (Probable). Adopts an amphipathic alpha helical conformation in membrane that is essential for the membrane disrupting activity (PubMed:23836163). Mast cell degranulator that induces a potent chemotaxis in polymorphonucleated leukocyte (PMNL) cells (PubMed:15052574, PubMed:15225564). Shows no or weak hemolytic activity (PubMed:15052574, PubMed:15225564).[1] [2] [3] [4] Publication Abstract from PubMedDespite the need for innovative compounds as antimicrobial and anticancer agents, natural sources of peptides remain underexplored. Protonectin (PTN), a cationic dodecapeptide of pharmacological interest, presents large hydrophobicity that is associated with the tendency to aggregate and supposedly influences bioactivity. A disaggregating role was assigned to PTN' N-terminal fragment (PTN1-6), which enhances the bioactivity of PTN in a 1:1 mixture (PTN/PTN1-6). Spectroscopic techniques and model membranes (phospholipid bilayers and SDS micelles) revealed that environment-dependent aggregation is reduced for PTN/PTN1-6, but cytotoxicity of PTNs on MDA-MB-231 breast cancer showed the same CC50 values around 16 microM and on MCF-10A epithelial breast cells 6 to 5-fold higher values, revealing a selective interaction. Since PTN1-6 lacks activity on breast cells, its presence should differently affect PTN activity, suggesting that aggregation could modulate activity depending on the membrane characteristics. Indeed, increased partitioning and lytic activity of PTN/PTN1-6 were found in model membranes independently of charge density, but affected by the curvature tendency. PTN and PTN/PTN1-6 do not alter morphology and roughness of cancer cells, indicating a superficial interaction with membranes and consistent with results obtained in NMR experiments. Our results indicate that aggregation of PTNs depends on the membrane characteristics and modulates the activity of the peptides. Protonectin peptides target lipids, act at the interface and selectively kill metastatic breast cancer cells while preserving morphological integrity.,Batista Martins D, Fadel V, Oliveira FD, Gaspar D, Alvares DS, Castanho MARB, Dos Santos Cabrera MP J Colloid Interface Sci. 2021 May 25;601:517-530. doi:, 10.1016/j.jcis.2021.05.115. PMID:34090029[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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