Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils

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Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils. / Сулацкая, Анна; Бондарев, Станислав Александрович; Сулацкий, Максим; Трубицина, Нина Павловна ; Белоусов, Михаил Владимирович ; Журавлева, Галина Анатольевна; Льянос, Мануэль; Каява, Андрей Вилхович; Кузнецова, Ирина; Туроверов, Константин.

в: Journal of Molecular Liquids, Том 314, 113618, 15.09.2020.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

BibTeX

@article{250c3354db2f4094bfe6d5939af71a57,

title = "Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils",

abstract = "We investigated the effect of the point substitutions in the N-terminal domain of the yeast prion protein Sup35 (Sup35NMp) on the structure of its amyloid fibrils. As the objects of the study, proteins with mutations that have different influence on the [PSI+] prion propagation, but do not prevent the aggregation of Sup35NMp in vitro were chosen. The use of the wide range of physicochemical methods allowed us to show significant differences in the structure of these aggregates, their physical size, clumping tendency. Also we demonstrated that the fluorescent probe thioflavin T (ThT) can be successfully used for investigation of subtle changes in the structural organization of fibrils formed from various Sup35NMp. The obtained results and our theoretical predictions allowed us to conclude that some of selected amino acid substitutions delimit the region of the protein that forms the core of amyloid fibrils, and change the fibrils structure. The relationship of structural features of in vitro Sup35NMp amyloid aggregates with the stability of the [PSI+] prion in vivo allowed us to suggest that oligopeptide repeats (R) of the amyloidogenic N-terminal domain of Sup35NMp from R0 to R2 play a key role in protein aggregation. Their arrangement rather than just presence is critical for propagation of the strong [PSI+] prion variants. The results confirm the suitability of the proposed combination of theoretical and empirical approaches for identifying changes in the amyloid fibrils structure, which, in turn, can significantly affect both the functional stability of amyloid fibrils and their pathogenicity.",

keywords = "Amyloid fibril, Beta-serpentine, Binding stoichiometry, Equilibrium microdialysis, Point mutation, Structural polymorphism, Sup35p, Super-pleated beta-structure, Thioflavin T, [PSI ] prion, [PSI+] prion, MOLECULAR-MECHANISM, DOMAIN, PSI+ PRION, THIOFLAVIN-T BINDING, SUP35 PROTEIN, IN-VITRO, BETA-SHEET, DISEASE, AGGREGATION, DETERMINANT PSI(+)",

author = "Анна Сулацкая and Бондарев, {Станислав Александрович} and Максим Сулацкий and Трубицина, {Нина Павловна} and Белоусов, {Михаил Владимирович} and Журавлева, {Галина Анатольевна} and Мануэль Льянос and Каява, {Андрей Вилхович} and Ирина Кузнецова and Константин Туроверов",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2020",

month = sep,

day = "15",

doi = "10.1016/j.molliq.2020.113618",

language = "English",

volume = "314",

journal = "Journal of Molecular Liquids",

issn = "0167-7322",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Point mutations affecting yeast prion propagation change the structure of its amyloid fibrils

AU - Сулацкая, Анна

AU - Бондарев, Станислав Александрович

AU - Сулацкий, Максим

AU - Трубицина, Нина Павловна

AU - Белоусов, Михаил Владимирович

AU - Журавлева, Галина Анатольевна

AU - Льянос, Мануэль

AU - Каява, Андрей Вилхович

AU - Кузнецова, Ирина

AU - Туроверов, Константин

PY - 2020/9/15

Y1 - 2020/9/15

N2 - We investigated the effect of the point substitutions in the N-terminal domain of the yeast prion protein Sup35 (Sup35NMp) on the structure of its amyloid fibrils. As the objects of the study, proteins with mutations that have different influence on the [PSI+] prion propagation, but do not prevent the aggregation of Sup35NMp in vitro were chosen. The use of the wide range of physicochemical methods allowed us to show significant differences in the structure of these aggregates, their physical size, clumping tendency. Also we demonstrated that the fluorescent probe thioflavin T (ThT) can be successfully used for investigation of subtle changes in the structural organization of fibrils formed from various Sup35NMp. The obtained results and our theoretical predictions allowed us to conclude that some of selected amino acid substitutions delimit the region of the protein that forms the core of amyloid fibrils, and change the fibrils structure. The relationship of structural features of in vitro Sup35NMp amyloid aggregates with the stability of the [PSI+] prion in vivo allowed us to suggest that oligopeptide repeats (R) of the amyloidogenic N-terminal domain of Sup35NMp from R0 to R2 play a key role in protein aggregation. Their arrangement rather than just presence is critical for propagation of the strong [PSI+] prion variants. The results confirm the suitability of the proposed combination of theoretical and empirical approaches for identifying changes in the amyloid fibrils structure, which, in turn, can significantly affect both the functional stability of amyloid fibrils and their pathogenicity.

AB - We investigated the effect of the point substitutions in the N-terminal domain of the yeast prion protein Sup35 (Sup35NMp) on the structure of its amyloid fibrils. As the objects of the study, proteins with mutations that have different influence on the [PSI+] prion propagation, but do not prevent the aggregation of Sup35NMp in vitro were chosen. The use of the wide range of physicochemical methods allowed us to show significant differences in the structure of these aggregates, their physical size, clumping tendency. Also we demonstrated that the fluorescent probe thioflavin T (ThT) can be successfully used for investigation of subtle changes in the structural organization of fibrils formed from various Sup35NMp. The obtained results and our theoretical predictions allowed us to conclude that some of selected amino acid substitutions delimit the region of the protein that forms the core of amyloid fibrils, and change the fibrils structure. The relationship of structural features of in vitro Sup35NMp amyloid aggregates with the stability of the [PSI+] prion in vivo allowed us to suggest that oligopeptide repeats (R) of the amyloidogenic N-terminal domain of Sup35NMp from R0 to R2 play a key role in protein aggregation. Their arrangement rather than just presence is critical for propagation of the strong [PSI+] prion variants. The results confirm the suitability of the proposed combination of theoretical and empirical approaches for identifying changes in the amyloid fibrils structure, which, in turn, can significantly affect both the functional stability of amyloid fibrils and their pathogenicity.

KW - Amyloid fibril

KW - Beta-serpentine

KW - Binding stoichiometry

KW - Equilibrium microdialysis

KW - Point mutation

KW - Structural polymorphism

KW - Sup35p

KW - Super-pleated beta-structure

KW - Thioflavin T

KW - [PSI ] prion

KW - [PSI+] prion

KW - MOLECULAR-MECHANISM

KW - DOMAIN

KW - PSI+ PRION

KW - THIOFLAVIN-T BINDING

KW - SUP35 PROTEIN

KW - IN-VITRO

KW - BETA-SHEET

KW - DISEASE

KW - AGGREGATION

KW - DETERMINANT PSI(+)

UR - http://www.scopus.com/inward/record.url?scp=85086996843&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/8e6ef16e-39f9-3fd5-8dcc-9b377e121cb9/

U2 - 10.1016/j.molliq.2020.113618

DO - 10.1016/j.molliq.2020.113618

M3 - Article

VL - 314

JO - Journal of Molecular Liquids

JF - Journal of Molecular Liquids

SN - 0167-7322

M1 - 113618

ER -

ID: 60423947