Solvent-induced Lag-phase on the Formation of Lysozyme Amyloid Fibrils Triggered by SDS: Biophysical Experimental and in Silico Study of Solvent Effects

Gabriel Zazeri*, Ana Ribeiro Povinelli, Nathalia M Pavan, Valdecir F Ximenes*, Alan M Jones*

*Corresponding author for this work

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Abstract

Amyloid aggregates arise from either the partial or complete loss of the native protein structure or the inability of proteins to attain their native conformation. These aggregates have been linked to several diseases, including Alzheimer’s, Parkinson’s, and lysozyme amyloidosis. A comprehensive dataset was recently reported, demonstrating the critical role of the protein’s surrounding environment in amyloid formation. In this study, we investigated the formation of lysozyme amyloid fibrils induced by sodium dodecyl sulfate (SDS) and the effect of solvents in the medium. Experimental data obtained through fluorescence spectroscopy revealed a notable lag phase in amyloid formation when acetone solution was present. This finding suggested that the presence of acetone in the reaction medium created an unfavorable microenvironment for amyloid fibril formation and impeded the organization of the denatured protein into the fibril form. The in silico data provided insights into the molecular mechanism of the interaction between acetone molecules and the lysozyme protofibril, once acetone presented the best experimental results. It was observed that the lysozyme protofibril became highly unstable in the presence of acetone, leading to the complete loss of its β-sheet conformation and resulting in an open structure. Furthermore, the solvation layer of the protofibril in acetone solution was significantly reduced compared to that in other solvents, resulting in fewer hydrogen bonds. Consequently, the presence of acetone facilitated the exposure of the hydrophobic portion of the protofibril, precluding the amyloid fibril formation. In summary, our study underscores the pivotal role the surrounding environment plays in influencing amyloid formation.
Original languageEnglish
Article number6891
Number of pages14
JournalMolecules
Volume28
Issue number19
DOIs
Publication statusPublished - 30 Sept 2023

Bibliographical note

Funding:
This work was financed by the National Council for Scientific and Technological Development (CNPq, Conselho Nacional de Desenvolvimento Científico e Tecnológico, #302121/2022‐6), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES, Finance Code 001), and the State of Sao Paulo Research Foundation (FAPESP, Fundação de Amparo a Pesquisa do Estado de São Paulo, #2019/18445‐5). Computational resources were obtained from the Federal Institute of Education, Science and Technology of Mato Grosso (IFMT), and the Center for Scientific Computing (NCC/GridUNESP) of São Paulo State University (UNESP), Brazil. We thank Molecules (MDPI) for a feature paper APC waiver.

Keywords

  • lysozyme
  • amyloid fibril
  • solvent effect
  • molecular biophysics

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