Аннотация
На конформационное поведение пептида амилоида-β42 (Aβ42) существенное влияние оказывает физическое состояние окружающего его липидного окружения. Влияние температуры на структуру Aβ42 в бислоях дипальмитоилфосфатидилхолина (DPPC) исследовалось с использованием методов кругового дихроизма (КД), рамановской спектроскопии и молекулярной динамики (МД). В исследовании рассматривались две температурные фазы: комнатная температура (RT ≈ (25±2)°C), соответствующая гель-фазе DPPC, и (48±2)°C, отвечающая жидкокристаллической фазе, выше температуры фазового перехода липидов. Измерения методом КД-спектроскопии показали явный температурно-зависимый структурный переход пептида. При комнатной температуре пептид Aβ42 характеризовался конформацией, обогащенной β-структурами, тогда как при температуре (48±2)°C спектры указывали на заметное увеличение доли α-спиралей, что свидетельствует об усилении упорядоченности полипептидной цепи в условиях жидкофазного состояния. Рамановский спектральный анализ подтвердил эту тенденцию, продемонстрировав увеличение вклада α-спиральных компонентов, сопровождающееся уменьшением доли β-структур при нагревании. Незначительные изменения колебательных маркеров липидов также указывали на повышенную гибкость ацильных цепей и возросшую текучесть бислоя в высокотемпературном состоянии. Кроме того, МД-моделирование выявило увеличение содержания α-спиральных структур и более глубокое внедрение пептидов в неупорядоченный бислой по сравнению с упорядоченной гелевой фазой. Результаты экспериментальных и вычислительных исследований показывают, что текучесть мембраны выше фазового перехода DPPC способствует стабилизации α-спиральной структуры Aβ42. Также подчёркивается важность температуры как ключевого параметра, который определяет конформационное равновесие между пептидами и липидами. Полученные результаты обеспечивают фундаментальную основу для понимания того, как температурные условия модулируют взаимодействия амилоида с мембраной, что важно для выяснения ранних молекулярных событий, связанных с патологиями, вызванными амилоидом.
Поддерживающие организации
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