dGAE(297-391) Tau Fragment Promotes Formation of Chronic
Traumatic Encephalopathy-Like Tau Filaments

J 2024

dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments

KITOKA, Kristine, Alons LENDS, Gytis KUČINSKAS, Anna Lina BULA, Lukas KRASAUSKAS et. al.

Základní údaje

Originální název

dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments

Autoři

KITOKA, Kristine, Alons LENDS, Gytis KUČINSKAS, Anna Lina BULA, Lukas KRASAUSKAS, Vytautas SMIRNOVAS, Monika ZILKOVA, Branislav KOVACECH, Rostislav SKRABANA, Jozef HRITZ a Kristaps JAUDZEMS

Vydání

Angewandte Chemie International Edition, WEINHEIM (GERMANY), Verlag Chemie, 2024, 1433-7851

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 16.600 v roce 2022

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1002/anie.202407821

UT WoS

001337992200001

Klíčová slova anglicky

tauopathies; tau protein; dGAE fragment; filamentous aggregates; NMR spectroscopy

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 11. 2024 15:15, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

The microtubule-associated protein tau forms disease-specific filamentous aggregates in several different neurodegenerative diseases. In order to understand how tau undergoes misfolding into a specific filament type and to control this process for drug development purposes, it is crucial to study in vitro tau aggregation methods and investigate the structures of the obtained filaments at the atomic level. Here, we used the tau fragment dGAE, which aggregates spontaneously, to seed the formation of full-length tau filaments. The structures of dGAE and full-length tau filaments were investigated by magic-angle spinning (MAS) solid-state NMR, showing that dGAE allows propagation of a chronic traumatic encephalopathy (CTE)-like fold to the full-length tau. The obtained filaments efficiently seeded tau aggregation in HEK293T cells. This work demonstrates that in vitro preparation of disease-specific types of full-length tau filaments is feasible.

Návaznosti

GF20-05789L, projekt VaV

Název: Charakterizace přirozeně neuspořádaných proteinů

Investor: Grantová agentura ČR, Characterization of intrinsically disordered proteins, Partnerská agentura (Rakousko)

LM2023042, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CIISB - Česká infrastruktura pro integrativní strukturní biologii

101087124, interní kód MU

Název: Alzheimer's Disease Diagnostics Innovation and Translation to Clinical Practice in Central Europe

Investor: Evropská unie, Alzheimer's Disease Diagnostics Innovation and Translation to Clinical Practice in Central Europe, Rozšiřování účasti a posílení ERA

873127, interní kód MU

Název: Integrative structural biology of pathological tau protein, an appealing therapeutic target for Alzheimer´s disease (Akronym: InterTAU)

Investor: Evropská unie, Integrative structural biology of pathological tau protein, an appealing therapeutic target for Alzheimer´s disease, MSCA Marie Skłodowska-Curie Actions (Excellent Science)

Citovat

KITOKA, Kristine, Alons LENDS, Gytis KUČINSKAS, Anna Lina BULA, Lukas KRASAUSKAS, Vytautas SMIRNOVAS, Monika ZILKOVA, Branislav KOVACECH, Rostislav SKRABANA, Jozef HRITZ a Kristaps JAUDZEMS. dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments. Angewandte Chemie International Edition. WEINHEIM (GERMANY): Verlag Chemie, 2024, 8 s. ISSN 1433-7851. Dostupné z: https://dx.doi.org/10.1002/anie.202407821.

@article{2449139,
   author = {Kitoka, Kristine and Lends, Alons and Kučinskas, Gytis and Bula, Anna Lina and Krasauskas, Lukas and Smirnovas, Vytautas and Zilkova, Monika and Kovacech, Branislav and Skrabana, Rostislav and Hritz, Jozef and Jaudzems, Kristaps},
   article_location = {WEINHEIM (GERMANY)},
   doi = {http://dx.doi.org/10.1002/anie.202407821},
   keywords = {tauopathies; tau protein; dGAE fragment; filamentous aggregates; NMR spectroscopy},
   language = {eng},
   issn = {1433-7851},
   journal = {Angewandte Chemie International Edition},
   title = {dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments},
   url = {https://onlinelibrary.wiley.com/doi/10.1002/anie.202407821},
   year = {2024}
}

TY  - JOUR
ID  - 2449139
AU  - Kitoka, Kristine - Lends, Alons - Kučinskas, Gytis - Bula, Anna Lina - Krasauskas, Lukas - Smirnovas, Vytautas - Zilkova, Monika - Kovacech, Branislav - Skrabana, Rostislav - Hritz, Jozef - Jaudzems, Kristaps
PY  - 2024
TI  - dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments
JF  - Angewandte Chemie International Edition
PB  - Verlag Chemie
SN  - 14337851
KW  - tauopathies
KW  - tau protein
KW  - dGAE fragment
KW  - filamentous aggregates
KW  - NMR spectroscopy
UR  - https://onlinelibrary.wiley.com/doi/10.1002/anie.202407821
N2  - The microtubule-associated protein tau forms disease-specific filamentous aggregates in several different neurodegenerative diseases. In order to understand how tau undergoes misfolding into a specific filament type and to control this process for drug development purposes, it is crucial to study in vitro tau aggregation methods and investigate the structures of the obtained filaments at the atomic level. Here, we used the tau fragment dGAE, which aggregates spontaneously, to seed the formation of full-length tau filaments. The structures of dGAE and full-length tau filaments were investigated by magic-angle spinning (MAS) solid-state NMR, showing that dGAE allows propagation of a chronic traumatic encephalopathy (CTE)-like fold to the full-length tau. The obtained filaments efficiently seeded tau aggregation in HEK293T cells. This work demonstrates that in vitro preparation of disease-specific types of full-length tau filaments is feasible.
ER  -

KITOKA, Kristine, Alons LENDS, Gytis KUČINSKAS, Anna Lina BULA, Lukas KRASAUSKAS, Vytautas SMIRNOVAS, Monika ZILKOVA, Branislav KOVACECH, Rostislav SKRABANA, Jozef HRITZ a Kristaps JAUDZEMS. dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments. \textit{Angewandte Chemie International Edition}. WEINHEIM (GERMANY): Verlag Chemie, 2024, 8 s. ISSN~1433-7851. Dostupné z: https://dx.doi.org/10.1002/anie.202407821.

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