Сибирский федеральный университет

Тип публикации: статья из журнала

Год издания: 2022

Идентификатор DOI: 10.3390/ijms232314645

Ключевые слова: amyloidogenesis, bovine carbonic anhydrase, protein folding pathway, time-resolved fluorescenceamyloid, 11061-24-8, carbonate dehydratase, 9001-03-0, amyloid, amyloidogenic proteins, carbonic anhydrase ii, carbonic anhydrases

Аннотация: Many proteins form amyloid fibrils only under conditions when the probability of transition from a native (structured, densely packed) to an intermediate (labile, destabilized) state is increased. It implies the assumption that some structural intermediates are more convenient for amyloid formation than the others. Hence, if a mutation affects the protein folding pathway, one should expect that this mutation could affect the rate of amyloid formation as well. In the current work, we have compared the effects of amino acid substitutions of bovine carbonic anhydrase II on its unfolding pathway and on its ability to form amyloids at acidic pH and an elevated temperature. Wild-type protein and four mutant forms (L78A, L139A, I208A, and M239A) were studied. We analyzed the change of the protein unfolding pathway by the time-resolved fluorescence technique and the process of amyloid formation by thioflavin T fluorescence assay and electron microscopy. It was revealed that I208A substitution accelerates amyloid formation and affects the structure of the late (molten globule-like)-intermediate state of carbonic anhydrase, whereas the other mutations slow down the growth of amyloids and have either no effect on the unfolding pathway (L78A, L139A) or alter the conformational states arising at the early unfolding stage (M239A). © 2022 by the authors.

Журнал: International Journal of Molecular Sciences

Выпуск журнала: Vol. 23, Is. 23

Номера страниц: 14645

ISSN журнала: 16616596

Издатель: MDPI

• Melnik B.S. (Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation, Pushchino Branch, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, 142290, Russian Federation)
• Katina N.S. (Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation)
• Ryabova N.A. (Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation)
• Marchenkov V.V. (Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation)
• Melnik T.N. (Institute of Protein Research, Russian Academy of Sciences, Pushchino, 142290, Russian Federation)
• Karuzina N.E. (Biophysics Department, Siberian Federal University, Krasnoyarsk, 660041, Russian Federation)
• Nemtseva E.V. (Biophysics Department, Siberian Federal University, Krasnoyarsk, 660041, Russian Federation, Institute of Biophysics, Siberian Branch of Russian Academy of Sciences, Krasnoyarsk, 660036, Russian Federation)

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