7pvb
Structure of Viscotoxin A3 from Viscum Album in the complex with DPC micellesStructure of Viscotoxin A3 from Viscum Album in the complex with DPC micelles
Structural highlights
FunctionTHN3_VISAL Thionins are small plant proteins which are toxic to animal cells. They seem to exert their toxic effect at the level of the cell membrane. Their precise function is not known. Publication Abstract from PubMedThionins are the family of small ( approximately 5 kDa) cationic cysteine-rich peptides involved in the immune response in plants. Viscotoxin A3 (VtA3) is the thionin from mistletoe (Viscum album) demonstrating antimicrobial and cytotoxic activity against cancer cells in vitro. VtA3 (charge +6) interacts with the membranes containing anionic lipids and forms cation-selective ion channels. Here we studied the VtA3 structure in membrane-mimicking media by NMR spectroscopy. Spatial structure of VtA3, consisting of a helical hairpin and a short beta-sheet, was stable and did not undergo significant changes during micelle binding. VtA3 molecule bound with high affinity to the surface of zwitterionic dodecylphosphocholine (DPC) micelle by hydrophobic patch in the helical hairpin. Oligomerization of VtA3 was observed in the anionic micelles of sodium dodecylsulphate (SDS). No direct contacts between the peptide molecules were observed and the possible interfaces of detergent-assisted oligomerization were revealed. The data obtained suggest that the VtA3 membrane activity, depending on the concentration, obeys the 'toroidal' pore model or the 'carpet' mechanism. The model of the membrane disrupting complex, which explains the ion channel formation in the partially anionic membranes, was proposed. Spatial structure and oligomerization of viscotoxin A3 in detergent micelles: Implication for mechanisms of ion channel formation and membrane lysis.,Paramonov AS, Lyukmanova EN, Tonevitsky AG, Arseniev AS, Shenkarev ZO Biochem Biophys Res Commun. 2021 Dec 31;585:22-28. doi:, 10.1016/j.bbrc.2021.11.022. Epub 2021 Nov 9. PMID:34781057[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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