Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Influence of Amino Acid Substitutions in ApoMb on Different Stages of Unfolding of Amyloids

Natalya Katina
* ORCID logo ,
Victor Marchenkov
ORCID logo ,
Natalya Ryabova
ORCID logo ,
Nelly Ilyina
,
Vitalii Balobanov
,
Alexey Finkelstein
* ORCID logo
Version 1 : Received: 4 November 2023 / Approved: 6 November 2023 / Online: 6 November 2023 (07:42:34 CET)

A peer-reviewed article of this Preprint also exists.

Katina, N.; Marchenkov, V.; Ryabova, N.; Ilyina, N.; Marchenko, N.; Balobanov, V.; Finkelstein, A. Influence of Amino Acid Substitutions in ApoMb on Different Stages of Unfolding of Amyloids. Molecules 2023, 28, 7736. Katina, N.; Marchenkov, V.; Ryabova, N.; Ilyina, N.; Marchenko, N.; Balobanov, V.; Finkelstein, A. Influence of Amino Acid Substitutions in ApoMb on Different Stages of Unfolding of Amyloids. Molecules 2023, 28, 7736.

Abstract

To date, most research on amyloid aggregation has focused on describing the structure of amyloids and the kinetics of their formation, while the conformational stability of fibrils remain insufficiently explored. The aim of this work was to investigate the effect of amino acid substitutions on the stability of apomyoglobin (ApoMb) amyloids. Study of amyloid unfolding of ApoMb and its six mutant variants by urea has been carried out. Changes in the structural features of aggregates during unfolding were recorded by the far UV CD and native electrophoresis. It was shown that during the initial stage of denaturation, amyloid's secondary structure partially unfolds. Then, the fibrils undergo dissociation and form intermediate aggregates weighing approximately 1 MDa, which at the last stage of unfolding decompose into 18 kDa monomeic unfolded molecules. The results of unfolding transitions allow concluding that the stability of studied amyloids relative to the intermediate aggregates and of the latter relative to unfolded monomers is higher for ApoMb variants with substitutions that increase the hydrophobicity of the residues. The results presented provide a new insight into the mechanism of stabilization of protein aggregates and can serve as a base for further investigations of the amyloids stability.

Keywords

apomyoglobin; amyloid stability; unfolding transition; native electrophoresis; hydrophobicity

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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