Key Factors Controlling Fibril Formation of Proteins

T.T.M. Thua, b, H.N.T. Phungc, N.T. Cod, A. Kloczkowskie, f, M.S. Lig aFaculty of Materials Science and Technology, University of Science — VNU HCM, 227 Nguyen Van Cu Street, District 5, Ho Chi Minh City, 700000 Vietnam bVietnam National University, Area 6, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, 700000 Vietnam cFaculty of Natural Sciences and Technology, Tay Nguyen University, 567 Le Duan street, Buon Me Thuot, Vietnam dFaculty of Chemistry, University of Gdańsk, Fahrenheit Union of Universities, Wita Stwosza 63, 80-308 Gdańsk, Poland eThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, 575 Children’s Crossroad, Columbus, Ohio 43215, USA fDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio 43215, USA gInstitute of Physics, Polish Academy of Sciences, al. Lotników 32/46, PL-02668, Warsaw, Poland

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Fibril formation resulting from protein aggregation is a hallmark of a large group of neurodegenerative human diseases, including Alzheimer’s disease, type 2 diabetes, amyotrophic lateral sclerosis, and Parkinson’s disease, among many others. Key factors governing protein fibril formation have been identified over the past decades to elucidate various facets of misfolding and aggregation. However, surprisingly little is known about how and why fibril structure is achieved, and it remains a fundamental problem in molecular biology. In this review, we discuss the relationship between fibril formation kinetics and various characteristics, including sequence, mutations, monomer secondary structure, mechanical stability of the fibril state, aromaticity, hydrophobicity, charge, and population of fibril-prone conformations in the monomeric state.

DOI:10.12693/APhysPolA.145.S21 topics: protein fibril formation, aggregation rate, neurodegenerative diseases, amyloid beta peptides