PXD056328

PXD056328 is an original dataset announced via ProteomeXchange.

Title	Structural recognition and stabilization of tyrosine hydroxylase by the J-domain protein DNAJC12
Description	Pathogenic variants of the J-domain protein DNAJC12, a co-chaperone of Hsp70, cause parkinsonism, which seems associated with a defective interaction of DNAJC12 with tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis. Here, we report the characterization of TH:DNAJC12 complex formation and show that DNAJC12 binding stabilizes TH and delays its time-dependent aggregation in an Hsp70-independent manner, while maintaining TH activity and regulatory inhibition by dopamine. Interestingly, although neither TH nor DNAJC12 alone significantly [MDT1] [AM2] activate Hsc70, the complex stimulates [AM3] its ATPase activity. Cryoelectron microscopy reveals two DNAJC12 monomers bound per TH tetramer, each embracing one of the two regulatory domain dimers, leaving all active sites available for substrate and dopamine interaction. Biochemical data confirm the key role of the DNAJC12 last eight residues in TH binding, explaining the molecular disease mechanism of C-terminal truncated DNAJC12 variants.
HostingRepository	PRIDE
AnnounceDate	2025-01-27
AnnouncementXML	Submission_2025-01-27_03:14:55.728.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jimena Muntaner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-27 06:29:51	ID requested
⏵ 1	2025-01-27 03:14:56	announced

Dataset with its publication pending

submitter keyword: TH, DNAJC12

José María Valpuesta
contact affiliation	National Center for Biotechnology (CNB-CSIC), Department of Macromolecular Structures)
contact email	jmv@cnb.csic.es
lab head
Jimena Muntaner
contact affiliation	Centro Nacional de Biotecnología (CNB-CSIC)
contact email	jimena.muntaner@cnb.csic.es
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/2025/01/PXD056328

PRIDE project URI

• PRIDE
  1. PXD056328
     1. Label: PRIDE project
     2. Name: Structural recognition and stabilization of tyrosine hydroxylase by the J-domain protein DNAJC12