PXD032037

PXD032037 is an original dataset announced via ProteomeXchange.

Title	Hsp multichaperone complex buffers pathologically modified Tau
Description	Alzheimer'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.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_05:38:55.632.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Henning Urlaub
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-03 11:49:02	ID requested
⏵ 1	2022-08-11 05:38:56	announced

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]

submitter keyword: Tau, Hsp, multichaperone, Alzheimer´s disease

Prof. Henning Urlaub
contact affiliation	Max 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 email	henning.urlaub@mpibpc.mpg.de
lab head
Henning Urlaub
contact affiliation	Max-Plank Institute for Biophysical Chemistry
contact email	msbio.goettingen@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/08/PXD032037

PRIDE project URI

• PRIDE
  1. PXD032037
     1. Label: PRIDE project
     2. Name: Hsp multichaperone complex buffers pathologically modified Tau