118013 20240319080945.0 doi 10.1038/s41467-022-32350-9 sideral 129511 ART-2022-129511 eng Gracia, Pablo Molecular mechanism for the synchronized electrostatic coacervation and co-aggregation of a-synuclein and tau 2022 Access copy available to the general public Unrestricted 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. info:eu-repo/grantAgreement/EC/H2020/813209/EU/Paramagnetic Species in Catalysis Research. A Unified Approach Towards Heterogeneous, Homogeneous and Enzyme Catalysis/PARACAT This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 813209-PARACAT info:eu-repo/grantAgreement/ES/MICINN-AEI/PGC2018-096335-B100 info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-109276RA-I00 info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-109306RB-I00 info:eu-repo/grantAgreement/ES/MICINN/RYC2018-026042-I info:eu-repo/grantAgreement/ES/UZ/CUD2019-BIO-01 info:eu-repo/grantAgreement/ES/UZ/CUD2020-BIO-01 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 16.6 2022 MULTIDISCIPLINARY SCIENCES 6 / 73 = 0.082 2022 Q1 T1 5.116 2022 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2022 Q1 Physics and Astronomy (miscellaneous) 2022 Q1 Chemistry (miscellaneous) 2022 Q1 24.9 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Polanco, David Universidad de Zaragoza (orcid)0000-0002-0005-6712 Tarancón-Díez, Jorge Serra, Ilenia Bracci, Maruan Universidad de Zaragoza (orcid)0000-0001-8310-8970 Oroz, Javier Laurents, Douglas V. García-Rubio, Inés Universidad de Zaragoza (orcid)0000-0002-1827-1250 Cremades, Nunilo Universidad de Zaragoza (orcid)0000-0002-9138-6687 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 2003 395 Universidad de Zaragoza Dpto. Física Materia Condensa. Área Física Materia Condensada 13 (2022), 4586 [16 pp.] Nature communications 2041-1723 4962757 http://zaguan.unizar.es/record/118013/files/texto_completo.pdf Versión publicada 2671764 http://zaguan.unizar.es/record/118013/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:118013 articulos driver 2024-03-18-12:30:21 ARTICLE