PXD063285

PXD063285 is an original dataset announced via ProteomeXchange.

Title	Proteolytic processing promotes the decatenation activity of human mitochondrial TOP3A; BioID
Description	The TOP3A gene encodes protein products that are targeted to both the nucleus and to mitochondria. The nuclear isoform of TOP3A is required for the resolution of double Holliday junctions during homologous recombination, while the mitochondrial isoform of TOP3A separates hemicatenated daughter mitochondrial DNA molecules following DNA replication. We have sought to identify differences between the two protein isoforms, and find that the mitochondrial isoform of TOP3A is truncated. This truncation is the result of proteolytic cleavage within the mitochondrial matrix that removes approximately 90 amino acids from the protein C-terminus. We identify MPP as the protease responsible and reconstitute the cleavage reaction in vitro, finding that the reaction can be blocked by mutation of the cleavage site. Removal of the C-terminus of TOP3A alters the biochemical activity of the enzyme, resulting in greater ssDNA binding and decatenation activity relative to the full-length protein. We propose that the truncation of TOP3A within mitochondria provides an adaptation of the enzyme that favours its ability to decatenate mtDNA substrates within mitochondria.
HostingRepository	PRIDE
AnnounceDate	2025-09-30
AnnouncementXML	Submission_2025-09-30_02:21:50.617.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ilian Atanassov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-24 07:11:38	ID requested
⏵ 1	2025-09-30 02:21:51	announced

Dataset with its publication pending

submitter keyword: TOP3A, label-free, BioID

Claes M Gustafsson
contact affiliation	Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg 405 30, Sweden.
contact email	claes.gustafsson@medkem.gu.se
lab head
Ilian Atanassov
contact affiliation	Max Planck Institute for Biology of Aging
contact email	ilian.atanassov@age.mpg.de
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/2025/09/PXD063285

PRIDE project URI

• PRIDE
  1. PXD063285
     1. Label: PRIDE project
     2. Name: Proteolytic processing promotes the decatenation activity of human mitochondrial TOP3A; BioID