Zweckstetter, Markus

[["dc.bibliographiccitation.firstpage","1545"],["dc.bibliographiccitation.issue","28"],["dc.bibliographiccitation.journal","Protein Science"],["dc.bibliographiccitation.lastpage","1551"],["dc.contributor.author","Oroz, Javier"],["dc.contributor.author","Blair, Laura J."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2019-11-27T13:35:15Z"],["dc.date.accessioned","2021-10-27T13:21:38Z"],["dc.date.available","2019-11-27T13:35:15Z"],["dc.date.available","2021-10-27T13:21:38Z"],["dc.date.issued","2019"],["dc.description.abstract","Hsp90 is an essential chaperone that requires large allosteric changes to determine its ATPase activity and client binding. The co-chaperone Aha1, which is the major ATPase stimulator in eukaryotes, is important for regulation of Hsp90's allosteric timing. Little is known, however, about the structure of the Hsp90/Aha1 complex. Here, we characterize the solution structure of unmodified human Hsp90/Aha1 complex using NMR spectroscopy. We show that the 214-kDa complex forms by a two-step binding mechanism and adopts multiple conformations in the absence of nucleotide. Aha1 induces structural changes near Hsp90's nucleotide-binding site, providing a basis for its ATPase-enhancing activity. Our data reveal important aspects of this pivotal chaperone/co-chaperone interaction and emphasize the relevance of characterizing dynamic chaperone structures in solution."],["dc.identifier.doi","10.1002/pro.3678"],["dc.identifier.isbn","31299134"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16757"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92037"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1469-896X"],["dc.relation.issn","1469-896X"],["dc.relation.issn","0961-8368"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Dynamic Aha1 co‐chaperone binding to human Hsp90"],["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"]]