PXD018701

PXD018701 is an original dataset announced via ProteomeXchange.

Title	Moyamoya disease factor RNF213 is a giant E3 ligase with a dynein-like core and a distinct ubiquitin-transfer mechanism
Description	RNF213 is the major susceptibility factor for Moyamoya disease, a progressive cerebrovascular disorder that often leads to brain stroke in adults and children. Characterization of disease-associated mutations has been complicated by the enormous size of RNF213. Here we present the cryo-EM structure of mouse RNF213. The structure reveals the intricate fold of the 584 kDa protein, comprising an N-terminal stalk, a dynein-like core with six ATPase units, and a multidomain E3 module. Collaboration with UbcH7, a cysteine-reactive E2, points to an unexplored ubiquitin-transfer mechanism that proceeds in a RING-independent manner. Moreover, we show that pathologic MMD mutations cluster in the composite E3 domain, likely interfering with substrate ubiquitination. In conclusion, the structure of RNF213 uncovers a distinct type of an E3 enzyme, highlighting the growing mechanistic diversity in ubiquitination cascades. Our results also provide the molecular framework for investigating the emerging role of RNF213 in lipid metabolism, hypoxia, and angiogenesis.
HostingRepository	PRIDE
AnnounceDate	2020-06-24
AnnouncementXML	Submission_2020-06-27_17:04:44.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018701
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Antonia Vogel
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Ammonia-loss; Glu->pyro-Glu; Oxidation; Acetyl; Carbamidomethyl; Gln->pyro-Glu
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-20 21:48:29	ID requested
1	2020-06-23 23:34:38	announced
⏵ 2	2020-06-27 17:04:45	announced	2020-06-28: Updated publication reference for PubMed record(s): 32573437.

Ahel J, Lehner A, Vogel A, Schleiffer A, Meinhart A, Haselbach D, Clausen T, Moyamoya disease factor RNF213 is a giant E3 ligase with a dynein-like core and a distinct ubiquitin-transfer mechanism. Elife, 9():(2020) [pubmed]

submitter keyword: RNF213, E3-ligase, Mouse

Tim Clausen
contact affiliation	IMP-Research Institute of Molecular Pathology Campus-Vienna-Biocenter 1 1030 Vienna
contact email	tim.clausen@imp.ac.at
lab head
Antonia Vogel
contact affiliation	IMP-Research Institute of Molecular Pathology
contact email	antonia.vogel@imp.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018701
     1. Label: PRIDE project
     2. Name: Moyamoya disease factor RNF213 is a giant E3 ligase with a dynein-like core and a distinct ubiquitin-transfer mechanism