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

doi:10.1016/j.ijbiomac.2022.12.104

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

Int J Biol Macromol. 2023 Feb 1:227:601-607. doi: 10.1016/j.ijbiomac.2022.12.104. Epub 2022 Dec 18.

Authors

Da Yeon Cheong¹, Seokbeom Roh¹, Insu Park², Yuxi Lin³, Young-Ho Lee⁴, Taeha Lee¹, Sang Won Lee⁵, Dongtak Lee⁵, Hyo Gi Jung⁶, Hyunji Kim⁶, Wonseok Lee⁷, Dae Sung Yoon⁸, Yoochan Hong⁹, Gyudo Lee¹⁰

Affiliations

¹ Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, South Korea; Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, South Korea.
² Department of Biomedical Engineering, Konyang University, Daejeon 35365, South Korea.
³ Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Ochang, Chungbuk 28119, South Korea.
⁴ Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Ochang, Chungbuk 28119, South Korea; Bio-Analytical Science, University of Science and Technology, Daejeon 34113, South Korea; Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, South Korea; Research Headquarters, Korea Brain Research Institute, Daegu 41068, South Korea.
⁵ School of Biomedical Engineering, Korea University, Seoul 02841, South Korea.
⁶ School of Biomedical Engineering, Korea University, Seoul 02841, South Korea; Interdisciplinary Program in Precision Public Health, Korea University, Seoul 02841, South Korea.
⁷ Department of Electrical Engineering, Korea National University of Transportation, Chungju 27469, South Korea.
⁸ School of Biomedical Engineering, Korea University, Seoul 02841, South Korea; Interdisciplinary Program in Precision Public Health, Korea University, Seoul 02841, South Korea; ASTRION Inc., Seoul 02841, South Korea. Electronic address: [email protected].
⁹ Department of Medical Devices, Korea Institute of Machinery and Materials (KIMM), Daegu 42994, South Korea. Electronic address: [email protected].
¹⁰ Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, South Korea; Interdisciplinary Graduate Program for Artificial Intelligence Smart Convergence Technology, Korea University, Sejong 30019, South Korea. Electronic address: [email protected].

PMID: 36543295
DOI: 10.1016/j.ijbiomac.2022.12.104

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.

Keywords: Amyloid proliferation; Amyloid stiffening; Atomic force microscopy; Pepsin; Proteolysis of amyloid.

MeSH terms

Amyloid* / metabolism
Amyloidogenic Proteins
Cell Proliferation
Circular Dichroism
Microscopy, Atomic Force
Pepsin A* / metabolism
Peptide Hydrolases / metabolism
Proteolysis

Substances

Pepsin A
Amyloid
Peptide Hydrolases
Amyloidogenic Proteins