6N68

NMR solution structure of Protonectin (Agelaia pallipes pallipes) interacting with SDS micelles: an antimicrobial peptide with anticancer activity on breast cancer cells

6N68 の概要

• エントリーDOI: 10.2210/pdb6n68/pdb
• NMR情報: BMRB: 30544
• 分子名称: Protonectin (1 entity in total)
• 機能のキーワード: anticancer activity, peptide membrane interaction, protonectin aggregation surface interaction, antitumor protein
• 由来する生物種: Agelaia pallipes pallipes (Neotropical social wasp)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1209.57

構造登録者

Fadel, V.,Martins, D.B.,Dos Santos Cabrera, M.P. (登録日: 2018-11-26, 公開日: 2020-06-03, 最終更新日: 2023-06-14)

主引用文献

Batista Martins, D.,Fadel, V.,Oliveira, F.D.,Gaspar, D.,Alvares, D.S.,Castanho, M.A.R.B.,Dos Santos Cabrera, M.P.
Protonectin peptides target lipids, act at the interface and selectively kill metastatic breast cancer cells while preserving morphological integrity.
J Colloid Interface Sci, 601:517-530, 2021

PubMed Abstract: Despite 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 (PTN), which enhances the bioactivity of PTN in a 1:1 mixture (PTN/PTN). Spectroscopic techniques and model membranes (phospholipid bilayers and SDS micelles) revealed that environment-dependent aggregation is reduced for PTN/PTN, but cytotoxicity of PTNs on MDA-MB-231 breast cancer showed the same CC values around 16 µM and on MCF-10A epithelial breast cells 6 to 5-fold higher values, revealing a selective interaction. Since PTN 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/PTN were found in model membranes independently of charge density, but affected by the curvature tendency. PTN and PTN/PTN 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.

PubMed: 34090029
DOI: 10.1016/j.jcis.2021.05.115

実験手法

SOLUTION NMR