Molecular mechanism for the synchronized electrostatic coacervation and co-aggregation of a-synuclein and tau

Gracia, Pablo ; Polanco, David (Universidad de Zaragoza) ; Tarancón-Díez, Jorge ; Serra, Ilenia ; Bracci, Maruan (Universidad de Zaragoza) ; Oroz, Javier ; Laurents, Douglas V. ; García-Rubio, Inés (Universidad de Zaragoza) ; Cremades, Nunilo (Universidad de Zaragoza)

Resumen: Amyloid aggregation of α-synuclein (αS) is the hallmark of Parkinson’s disease and other synucleinopathies. Recently, Tau protein, generally associated with Alzheimer’s disease, has been linked to αS pathology and observed to co- localize in αS-rich disease inclusions, although the molecular mechanisms for the co-aggregation of both proteins remain elusive. We report here that αS phase-separates into liquid condensates by electrostatic complex coacerva- tion with positively charged polypeptides such as Tau. Condensates undergo either fast gelation or coalescence followed by slow amyloid aggregation depending on the affinity of αS for the poly-cation and the rate of valence exhaustion of the condensate network. By combining a set of advanced bio- physical techniques, we have been able to characterize αS/Tau liquid-liquid phase separation and identified key factors that lead to the formation of hetero-aggregates containing both proteins in the interior of the liquid protein condensates.

Idioma: Inglés

DOI: 10.1038/s41467-022-32350-9

Año: 2022

Publicado en: Nature communications 13 (2022), 4586 [16 pp.]
ISSN: 2041-1723

Factor impacto JCR: 16.6 (2022)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 6 / 73 = 0.082 (2022) - Q1 - T1

Factor impacto CITESCORE: 24.9 - Physics and Astronomy (Q1) - General (Q1) - Chemistry (Q1) - Biochemistry, Genetics and Molecular Biology (Q1)

Factor impacto SCIMAGO: 5.116 - Biochemistry, Genetics and Molecular Biology (miscellaneous) (Q1) - Physics and Astronomy (miscellaneous) (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/813209/EU/Paramagnetic Species in Catalysis Research. A Unified Approach Towards Heterogeneous, Homogeneous and Enzyme Catalysis/PARACAT
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PGC2018-096335-B100
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-109276RA-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-109306RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC2018-026042-I
Financiación: info:eu-repo/grantAgreement/ES/UZ/CUD2019-BIO-01
Financiación: info:eu-repo/grantAgreement/ES/UZ/CUD2020-BIO-01

Tipo y forma: Article (Published version)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Física Materia Condensada (Dpto. Física Materia Condensa.)