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PXD032037 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHsp multichaperone complex buffers pathologically modified Tau
DescriptionAlzheimer's disease is a neurodegenerative disorder in which misfolding and aggregation of pathologically modified Tau is critical for neuronal dysfunction and degeneration. The two central chaperones Hsp70 and Hsp90 coordinate protein homeostasis, but the nature of the interaction of Tau with the Hsp70/Hsp90 machinery has remained enigmatic. Here we show that Tau is a high-affinity substrate of the human Hsp70/Hsp90 machinery forming a 710 kDa client-loading complex. Complex formation involves extensive intermolecular contacts, blocks Tau aggregation and depends on Tau’s aggregation-prone repeat region. The Hsp90 co-chaperone p23 directly binds Tau and stabilizes the multichaperone/substrate complex, whereas the E3 ubiquitin-protein ligase CHIP efficiently disassembles the machinery targeting Tau to proteasomal degradation. Because phosphorylated Tau binds the Hsp70/Hsp90 machinery but is not recognized by Hsp90 alone, the data establish the Hsp70/Hsp90 multichaperone complex as a critical regulator of Tau in neurodegenerative disorders.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHenning Urlaub
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-03-03 11:49:02ID requested
12022-08-11 05:38:56announced
Publication List
Moll A, Ramirez LM, Ninov M, Schwarz J, Urlaub H, Zweckstetter M, Hsp multichaperone complex buffers pathologically modified Tau. Nat Commun, 13(1):3668(2022) [pubmed]
Keyword List
submitter keyword: Tau, Hsp, multichaperone, Alzheimer´s disease
Contact List
Prof. Henning Urlaub
contact affiliationMax Planck Institute for Multidisciplinary Sciences, Bioanalytical Mass Spectrometry Group, Am Fassberg 11, 37077 Göttingen, Germany University Medical Center Goettingen, Institute for Clinical Chemistry, Bioanalytics, Robert-Koch-Strasse 40, 37075 Göttingen, Germany
contact emailhenning.urlaub@mpibpc.mpg.de
lab head
Henning Urlaub
contact affiliationMax-Plank Institute for Biophysical Chemistry
contact emailmsbio.goettingen@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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