Biochem Biophys Res Commun, 2021, 585:22-28

Spatial structure and oligomerization of viscotoxin A3 in detergent micelles: Implication for mechanisms of ion channel formation and membrane lysis

Thionins are the family of small (∼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 β-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.

IBCH: 9566
Ссылка на статью в журнале: https://linkinghub.elsevier.com/retrieve/pii/S0006291X21015254
Кол-во цитирований на 07.2024: 2
Данные статьи проверены модераторами 2021-11-17

Список научных проектов, где отмечена публикация

  1. Структурная биология мембранных белков для создания новых лекарственных и диагностических средств (1 Июня 2019 года — 31 Декабря 2022 года). Арсеньев А.С., Бочаров Э.В., Минеев К.С., Шенкарёв З.О., Артемьева Л.Е., Бершацкий Я.В., Волынский П.Е., Гончарук М.В., Гончарук С.А., Гороховатский А.Ю., Ефремов Р.Г., Заняткин И.А., Игнатова А.А., Коваленко В.Р., Кот Э.Ф., Кочаровская М.В., Крылов Н.А., Кузнецов А.С., Лесовой Д.М., Лушпа В.А., Мышкин М.Ю., Некрасова О.В., Панина И.С., Урбан А.С., Шломина А.И., Шулепко М.А.. Грант, РНФ.