TY - JOUR

T1 - Spontaneous formation of different forms of alpha-synuclein fibrils from a recombinant protein

AU - Egorov, V.V.

AU - Grudinina, N.A.

AU - Polyakov, D.S.

AU - Zabrodskaya, Y.A.

AU - Gavrilova, N.V.

AU - Shavlovsky, M.M.

N1 - Export Date: 01 November 2025; Cited By: 0; Correspondence Address: V.V. Egorov; Federal State Budgetary Scientific Institution ‘Institute of Experimental Medicine’, St. Petersburg, Akademika Pavlova Street 12, 197022, Russian Federation; email: sondyn@yandex.ru; CODEN: BBRCA

PY - 2024

Y1 - 2024

N2 - Alpha-synuclein is a protein, the conformational changes of which lead to the development of such socially significant diseases as Parkinson's disease and amyotrophic lateral sclerosis. The methods for differential diagnostics of these diseases based on the use of alpha-synuclein in a non-native conformation obtained from patients as a seed for inducing fibrillogenesis and studying the morphology of the resulting amyloid-like fibrils were described in a number of studies. The authors associate such properties of the seed with the presence of post-translational modifications in the protein obtained from patients. At the same time, the production of fibrils differing in morphology from recombinant alpha-synuclein under various conditions of fibrillogenesis is also described. In this work, we show that the formation of morphologically distinct fibril types from recombinant alpha-synuclein lacking post-translational modifications is possible under the same conditions, and that spontaneously arising different fibril types, when used as a seed for fibrillogenesis, lead to the formation of recombinant protein fibrils morphological similar to the parental seed. The results of the work can be used both in studying the fundamental mechanisms of conformation transfer and in developing test systems for synucleinopathies. © 2024 Elsevier B.V., All rights reserved.

AB - Alpha-synuclein is a protein, the conformational changes of which lead to the development of such socially significant diseases as Parkinson's disease and amyotrophic lateral sclerosis. The methods for differential diagnostics of these diseases based on the use of alpha-synuclein in a non-native conformation obtained from patients as a seed for inducing fibrillogenesis and studying the morphology of the resulting amyloid-like fibrils were described in a number of studies. The authors associate such properties of the seed with the presence of post-translational modifications in the protein obtained from patients. At the same time, the production of fibrils differing in morphology from recombinant alpha-synuclein under various conditions of fibrillogenesis is also described. In this work, we show that the formation of morphologically distinct fibril types from recombinant alpha-synuclein lacking post-translational modifications is possible under the same conditions, and that spontaneously arising different fibril types, when used as a seed for fibrillogenesis, lead to the formation of recombinant protein fibrils morphological similar to the parental seed. The results of the work can be used both in studying the fundamental mechanisms of conformation transfer and in developing test systems for synucleinopathies. © 2024 Elsevier B.V., All rights reserved.

KW - alpha synuclein

KW - recombinant protein

KW - restriction endonuclease

KW - yellow fluorescent protein

KW - amyloid

KW - amino acid sequence

KW - Article

KW - binding site

KW - conformational transition

KW - denaturing gradient gel electrophoresis

KW - development

KW - enzymatic hydrolysis

KW - Escherichia coli

KW - fibril

KW - fibrillogenesis

KW - fluorescence intensity

KW - fluorometry

KW - gene insertion

KW - gene sequence

KW - mass spectrometry

KW - morphology

KW - polyacrylamide gel electrophoresis

KW - protein aggregation

KW - protein conformation

KW - protein degradation

KW - protein processing

KW - protein purification

KW - protein structure

KW - protein synthesis

KW - reading frame

KW - synucleinopathy

KW - transmission electron microscopy

KW - chemistry

KW - genetics

KW - human

KW - metabolism

KW - alpha-Synuclein

KW - Amyloid

KW - Humans

KW - Protein Conformation

KW - Protein Processing, Post-Translational

KW - Recombinant Proteins

U2 - 10.1016/j.bbrc.2024.151068

DO - 10.1016/j.bbrc.2024.151068

M3 - статья

VL - 741

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

ER -