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PXD014282 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructure of the Fanconi anaemia monoubiquitin ligase complex
DescriptionThe Fanconi Anemia (FA) pathway repairs DNA damage caused by endogenous and chemotherapy-induced DNA crosslinks. Genetic inactivation of this pathway impairs development, prevents blood production and promotes cancer. The key molecular step in the FA pathway is the monoubiquitination of a heterodimer of FANCI-FANCD2 by the FA core complex - a megadalton multiprotein E3 ubiquitin ligase. Monoubiquitinated FANCI-FANCD2 then activates a pathway to remove the DNA crosslink. Lack of molecular insight into the FA core complex limits a detailed explanation of how this vital DNA repair pathway functions. Here we reconstituted an active, recombinant FA core complex, and used electron cryo-microscopy (cryo-EM) and mass spectrometry to determine its overall structure. The FA core complex is comprised of a central symmetric dimer of the FANCB and FAAP100 subunits, flanked by two copies of the RING finger protein, FANCL. This acts as a scaffold to assemble the remaining five subunits, resulting in an extended asymmetric structure. The two FANCL subunits are positioned at opposite ends of the complex in an unusual asymmetric arrangement, distinct from other E3 ligases. We propose that each of the two FANCL subunits play unique roles within the complex ??? one is a structural component while the other monoubiquitinates FANCD2. The cryo-EM structure of the FA core complex, supported by crosslinking mass spectrometry and native mass spectrometry, therefore provides a foundation for a detailed understanding of this fundamental DNA repair pathway.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFrancis O'Reilly
SpeciesList scientific name: Gallus gallus (Chicken); NCBI TaxID: 9031;
ModificationListcarbamoylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-06-18 01:35:05ID requested
12019-10-16 02:05:36announced
22019-11-08 00:42:46announced2019-11-08: Updated publication reference for PubMed record(s): 31666700.
32019-11-27 06:00:00announced2019-11-27: Updated project metadata.
Publication List
Shakeel S, Rajendra E, Alc, รณ, n P, O'Reilly F, Chorev DS, Maslen S, Degliesposti G, Russo CJ, He S, Hill CH, Skehel JM, Scheres SHW, Patel KJ, Rappsilber J, Robinson CV, Passmore LA, Structure of the Fanconi anaemia monoubiquitin ligase complex. Nature, 575(7781):234-237(2019) [pubmed]
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: Fanconi anemia monoubiquitin ligase, human, crosslinking MS, CLMS, Electron microscopy, EM
Contact List
Juri Rappsilber
contact affiliationBioanalytics, Institute of Biotechnology, Technische Universit??t Berlin, 13355 Berlin, Germany Wellcome Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, Scotland, United Kingdom
contact emailjuri.rappsilber@tu-berlin.de
lab head
Francis O'Reilly
contact affiliationTU Berlin
contact emailoreilly@tu-berlin.de
dataset submitter
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Dataset FTP location
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