Proteolysis-driven proliferation and rigidification of pepsin-resistant amyloid fibrils

Da Yeon Cheong, Seokbeom Roh, Insu Park, Yuxi Lin, Young Ho Lee, Taeha Lee, Sang Won Lee, Dongtak Lee, Hyo Gi Jung, Hyunji Kim, Wonseok Lee, Dae Sung Yoon, Yoochan Hong, Gyudo Lee

    Research output: Contribution to journalArticlepeer-review

    8 Citations (Scopus)

    Abstract

    Proteolysis of amyloids is related to prevention and treatment of amyloidosis. What if the conditions for proteolysis were the same to those for amyloid formation? For example, pepsin, a gastric protease is activated in an acidic environment, which, interestingly, is also a condition that induces the amyloid formation. Here, we investigate the competition reactions between proteolysis and synthesis of amyloid under pepsin-activated conditions. The changes in the quantities and nanomechanical properties of amyloids after pepsin treatment were examined by fluorescence assay, circular dichroism and atomic force microscopy. We found that, in the case of pepsin-resistant amyloid, a secondary reaction can be accelerated, thereby proliferating amyloids. Moreover, after this reaction, the amyloid became 32.4 % thicker and 24.2 % stiffer than the original one. Our results suggest a new insight into the proteolysis-driven proliferation and rigidification of pepsin-resistant amyloids.

    Original languageEnglish
    Pages (from-to)601-607
    Number of pages7
    JournalInternational Journal of Biological Macromolecules
    Volume227
    DOIs
    Publication statusPublished - 2023 Feb 1

    Bibliographical note

    Publisher Copyright:
    © 2022

    Keywords

    • Amyloid proliferation
    • Amyloid stiffening
    • Atomic force microscopy
    • Pepsin
    • Proteolysis of amyloid

    ASJC Scopus subject areas

    • Structural Biology
    • Biochemistry
    • Molecular Biology

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