A new fibrillization mechanism of ß-lactoglobulin in glycine solutions

Jaklin, Matej (author), Hritz, Jozef (author), Hribar-Lee, Barbara (author)

Even though amyloid aggregates were discovered many years ago the mechanism of their formation is still a mystery. Because of their connection to many of untreatable neurodegenerative diseases the motivation for finding a common aggregation path is high. We report a new high heat induced fibrillization path of a model protein β-lactoglobulin (BLG) when incubated in glycine instead of water at pH 2. By combining atomic force microscopy (AFM), transmission emission microscopy (TEM), dynamic light scattering (DLS) and circular dichroism (CD) we predict that the basic building blocks of fibrils made in glycine are not peptides, but rather spheroid oligomers of different height that form by stacking of ring-like structures. Spheroid oligomers linearly align to form fibrils by opening up and combining. We suspect that glycine acts as an hydrolysation inhibitor which consequently promotes a different fibrillization path. By combining the known data on fibrillization in water with our experimental conclusions we come up with a new fibrillization scheme for BLG. We show that by changing the fibrillization conditions just by small changes in buffer composition can dramatically change the aggregation pathway and the effect of buffer shouldn't be neglected. Fibrils seen in our study are also gaining more and more attention because of their pore-like structure and a possible cytotoxic mechanism by forming pernicious ion-channels. By preparing them in a simple model system as BLG we opened a new way to study their formation.

• Language: English
• Keywords: ß-lactoglobulin, fibrillization mechanism, buffer specific effects, spheroid oligomers
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 414-425
• Numbering: Vol. 216
• PID: 20.500.12556/RUL-138811
• UDC: 577.322
• ISSN on article: 0141-8130
• DOI: 10.1016/j.ijbiomac.2022.06.182
• COBISS.SI-ID: 114740483
• Publication date in RUL: 19.08.2022

Record is a part of a journal

• Title: International journal of biological macromolecules
• Shortened title: Int. j. biol. macromol.
• Publisher: Elsevier
• ISSN: 0141-8130
• COBISS.SI-ID: 25637888

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: ß-laktoglobulin, fibrilizacijski mehanizem, pufer specifični efekt, sferoidni oligomeri