PXD013085

PXD013085 is an original dataset announced via ProteomeXchange.

Title	Dishevelled-3 protein conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1
Description	Dishevelled (DVL) is the key component of the Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions is unknown. To overcome this limitation, we developed the Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study DVL conformation in living cells. Using this single-cell FRET approach, we demonstrate that (i) Wnt ligands induce open DVL conformation, (ii) DVL variants that are predominantly open, show more even subcellular localization and more efficient membrane recruitment by Frizzled (FZD) and (iii) Casein Kinase 1 ɛ (CK1ɛ) has a key regulatory function in DVL conformational dynamics. In silico modeling and in vitro biophysical methods explain how CK1ɛ-specific phosphorylation events control DVL conformations via modulation of the PDZ domain and its interaction with DVL C-terminus. In summary, our study describes an experimental tool for DVL conformational sampling in living cells and elucidates the essential regulatory role of CK1ɛ in DVL conformational dynamics.
HostingRepository	PRIDE
AnnounceDate	2019-04-02
AnnouncementXML	Submission_2019-04-23_02:43:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katerina Hanáková
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-13 07:00:47	ID requested
1	2019-04-02 08:32:16	announced
⏵ 2	2019-04-23 02:43:40	announced	Updated publication reference for PubMed record(s): 31000703.

Harno, š J, Ca, ñ, izal MCA, Jur, á, sek M, Kumar J, Holler C, Schambony A, Han, á, kov, á K, Bernat, í, k O, Zdr, á, hal Z, G, ö, m, ö, ryov, á K, Gybe, ľ T, Radaszkiewicz TW, Kravec M, Trant, í, rek L, Ryne, š J, Dave Z, Fern, á, ndez-Llamazares AI, V, á, cha R, Tripsianes K, Hoffmann C, Bryja V, Dishevelled-3 conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1. Nat Commun, 10(1):1804(2019) [pubmed]

submitter keyword: Dishevelled, conformation, FlAsH-based FRET approach, phosphorylation, casein kinase 1 ɛ

Zbynek Zdrahal
contact affiliation	National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic; Proteomics Core facility, Masaryk University, Brno, Czech Republic
contact email	zdrahal@sci.muni.cz
lab head
Katerina Hanáková
contact affiliation	CEITEC MU
contact email	katerina.hanak@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/2019/04/PXD013085

PRIDE project URI

• PRIDE
  1. PXD013085
     1. Label: PRIDE project
     2. Name: Dishevelled-3 protein conformation dynamics analyzed by FRET-based biosensors reveals a key role of casein kinase 1