PXD011510

PXD011510 is an original dataset announced via ProteomeXchange.

Title	Critical role of the UBL-domain in stimulating the E3 ubiquitin ligase activity of UHRF1 towards chromatin
Description	The RING E3 ubiquitin ligase UHRF1 controls DNA methylation through its ability to target the maintenance DNA methyltransferase DNMT1 to newly replicated chromatin. DNMT1 recruitment relies on ubiquitylation of histone H3 by UHRF1, however, how UHRF1 deposits ubiquitin onto the histone is unknown. Here, we demonstrate that the ubiquitin-like domain (UBL) of UHRF1 is essential for RINGmediated H3 ubiquitylation. Using chemical crosslinking and mass spectrometry, biochemical assays and recombinant chromatin substrates we show that the UBL participates in structural rearrangements of UHRF1 upon binding to chromatin and the E2 ubiquitin conjugating enzyme UbcH5a/UBE2D1. Similar to ubiquitin, the UBL exerts its effects through a hydrophobic patch that contacts a regulatory surface on the “backside” of the E2 to stabilise the E2-E3-chromatin complex. Our analysis of the enzymatic mechanism of UHRF1 uncovers an unexpected function of the UBLdomain and defines a new role for this domain in DNMT1-dependent inheritance of DNA methylation.
HostingRepository	PRIDE
AnnounceDate	2018-11-04
AnnouncementXML	Submission_2018-11-20_01:15:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Holger Kramer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine; propanoyl labeling reagent light form (N-term); propanoylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-29 07:11:46	ID requested
1	2018-11-04 15:40:44	announced
⏵ 2	2018-11-20 01:15:50	announced	Updated publication reference for PubMed record(s): 30392929.

Foster BM, Stolz P, Mulholland CB, Montoya A, Kramer H, Bultmann S, Bartke T, Ubiquitin Ligase Activity of UHRF1 toward Chromatin. Mol Cell, 72(4):739-752.e9(2018) [pubmed]

curator keyword: Biological

submitter keyword: UHRF1, chromatin, ubiquitylation, Ubiquitin-like fold, DNA methylation, Histone modification

Till Bartke
contact affiliation	Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Ingolstädter Landstr. 1 D-85764 Neuherberg Germany
contact email	till.bartke@helmholtz-muenchen.de
lab head
Holger Kramer
contact affiliation	MRC London Institute of Medical Sciences
contact email	h.kramer@lms.mrc.ac.uk
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/2018/11/PXD011510

PRIDE project URI

• PRIDE
  1. PXD011510
     1. Label: PRIDE project
     2. Name: Critical role of the UBL-domain in stimulating the E3 ubiquitin ligase activity of UHRF1 towards chromatin