Zweckstetter, Markus

[["dc.bibliographiccitation.firstpage","6503"],["dc.bibliographiccitation.issue","26"],["dc.bibliographiccitation.journal","Chemical Science"],["dc.bibliographiccitation.lastpage","6507"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Ambadipudi, Susmitha"],["dc.contributor.author","Reddy, Jithender G."],["dc.contributor.author","Biernat, Jacek"],["dc.contributor.author","Mandelkow, Eckhard"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2019-09-30T09:26:49Z"],["dc.date.accessioned","2021-10-27T13:21:20Z"],["dc.date.available","2019-09-30T09:26:49Z"],["dc.date.available","2021-10-27T13:21:20Z"],["dc.date.issued","2019"],["dc.description.abstract","Liquid-liquid phase separation (LLPS) of proteins enables the formation of non-membrane-bound organelles in cells and is associated with cancer and neurodegeneration. Little is known however about the structure and dynamics of proteins in LLPS conditions, because of the polymorphic nature of liquid-like protein droplets. Using carbon-detected NMR experiments we here show that the conversion of the aggregation-prone repeat region of the Alzheimer's-related protein tau from the dispersed monomeric state to phase-separated liquid-like droplets involves tau's aggregation-prone hexapeptides and regulatory KXGS motifs. Droplet dissolution in presence of 1,6-hexanediol revealed that chemical shift perturbations in the hexapeptide motifs are temperature driven, while those in KXGS motifs report on phase separation. Residue-specific secondary structure analysis further indicated that tau's repeat region exists in extended conformation in the dispersed state and attains transient β-hairpin propensity upon LLPS. Taken together our work shows that NMR spectroscopy can provide high-resolution insights into LLPS-induced changes in intrinsically disordered proteins."],["dc.identifier.doi","10.1039/C9SC00531E"],["dc.identifier.pmid","31341602"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16419"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92013"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2041-6539"],["dc.relation.issn","2041-6520"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/3.0"],["dc.subject.ddc","610"],["dc.title","Residue-specific identification of phase separation hot spots of Alzheimer's-related protein tau"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","4532"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Oroz, Javier"],["dc.contributor.author","Chang, Bliss J."],["dc.contributor.author","Wysoczanski, Piotr"],["dc.contributor.author","Lee, Chung-Tien"],["dc.contributor.author","Pérez-Lara, Ángel"],["dc.contributor.author","Chakraborty, Pijush"],["dc.contributor.author","Hofele, Romina V."],["dc.contributor.author","Baker, Jeremy D."],["dc.contributor.author","Blair, Laura J."],["dc.contributor.author","Biernat, Jacek"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Mandelkow, Eckhard"],["dc.contributor.author","Dickey, Chad A."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2019-07-09T11:50:23Z"],["dc.date.available","2019-07-09T11:50:23Z"],["dc.date.issued","2018"],["dc.description.abstract","The molecular chaperone Hsp90 is critical for the maintenance of cellular homeostasis and represents a promising drug target. Despite increasing knowledge on the structure of Hsp90, the molecular basis of substrate recognition and pro-folding by Hsp90/co-chaperone complexes remains unknown. Here, we report the solution structures of human full-length Hsp90 in complex with the PPIase FKBP51, as well as the 280 kDa Hsp90/FKBP51 complex bound to the Alzheimer's disease-related protein Tau. We reveal that the FKBP51/Hsp90 complex, which synergizes to promote toxic Tau oligomers in vivo, is highly dynamic and stabilizes the extended conformation of the Hsp90 dimer resulting in decreased Hsp90 ATPase activity. Within the ternary Hsp90/FKBP51/Tau complex, Hsp90 serves as a scaffold that traps the PPIase and nucleates multiple conformations of Tau's proline-rich region next to the PPIase catalytic pocket in a phosphorylation-dependent manner. Our study defines a conceptual model for dynamic Hsp90/co-chaperone/client recognition."],["dc.identifier.doi","10.1038/s41467-018-06880-0"],["dc.identifier.pmid","30382094"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15928"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59763"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/626526/EU//HSP70-TAU NMR"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/283570/EU//BIOSTRUCT-X"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Structure and pro-toxic mechanism of the human Hsp90/PPIase/Tau complex"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]