PXD024358-1

PXD024358 is an original dataset announced via ProteomeXchange.

Title	Gel-like inclusions of C-terminal fragments of TDP-43 sequester and inhibit proteasomes
Description	TDP-43 inclusions enriched in C-terminal terminal fragments of ~25 kDa ("TDP-25") are associated with neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we analyzed gain-of-function mechanisms of TDP-25 combining cryo-electron tomography, proteomics and functional assays. We show that TDP-25 inclusions are amorphous with gel-like properties. Inclusions sequester proteasomes adopting exclusively substrate-processing conformations. This leads to proteostasis impairment, further enhanced by pathogenic mutations. These findings bolster the importance of proteasome dysfunction in ALS/FTD.
HostingRepository	PRIDE
AnnounceDate	2022-04-14
AnnouncementXML	Submission_2022-04-14_06:53:48.570.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-24 07:13:04	ID requested
⏵ 1	2022-04-14 06:53:48	announced

Dataset with its publication pending

submitter keyword: TDP-43, ALS, FTD, proteomics, proteasomes

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024358
     1. Label: PRIDE project
     2. Name: Gel-like inclusions of C-terminal fragments of TDP-43 sequester and inhibit proteasomes