Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure of the Fanconi anaemia monoubiquitin ligase complex.
Journal, issue, pages	Nature, Vol. 575, Issue 7781, Page 234-237, Year 2019
Publish date	Oct 30, 2019
Authors	Shabih Shakeel / Eeson Rajendra / Pablo Alcón / Francis O'Reilly / Dror S Chorev / Sarah Maslen / Gianluca Degliesposti / Christopher J Russo / Shaoda He / Chris H Hill / J Mark Skehel / Sjors H W Scheres / Ketan J Patel / Juri Rappsilber / Carol V Robinson / Lori A Passmore /
PubMed Abstract	The Fanconi anaemia (FA) pathway repairs DNA damage caused by endogenous and chemotherapy-induced DNA crosslinks, and responds to replication stress. Genetic inactivation of this pathway by mutation ...The Fanconi anaemia (FA) pathway repairs DNA damage caused by endogenous and chemotherapy-induced DNA crosslinks, and responds to replication stress. Genetic inactivation of this pathway by mutation of genes encoding FA complementation group (FANC) proteins impairs development, prevents blood production and promotes cancer. The key molecular step in the FA pathway is the monoubiquitination of a pseudosymmetric heterodimer of FANCD2-FANCI by the FA core complex-a megadalton multiprotein E3 ubiquitin ligase. Monoubiquitinated FANCD2 then recruits additional protein factors to remove the DNA crosslink or to stabilize the stalled replication fork. A molecular structure of the FA core complex would explain how it acts to maintain genome stability. Here we reconstituted an active, recombinant FA core complex, and used cryo-electron microscopy and mass spectrometry to determine its structure. The FA core complex comprises two central dimers of the FANCB and FA-associated protein of 100 kDa (FAAP100) subunits, flanked by two copies of the RING finger subunit, FANCL. These two heterotrimers act as a scaffold to assemble the remaining five subunits, resulting in an extended asymmetric structure. Destabilization of the scaffold would disrupt the entire complex, resulting in a non-functional FA pathway. Thus, the structure provides a mechanistic basis for the low numbers of patients with mutations in FANCB, FANCL and FAAP100. Despite a lack of sequence homology, FANCB and FAAP100 adopt similar structures. The two FANCL subunits are in different conformations at opposite ends of the complex, suggesting that each FANCL has a distinct role. This structural and functional asymmetry of dimeric RING finger domains may be a general feature of E3 ligases. The cryo-electron microscopy structure of the FA core complex provides a foundation for a detailed understanding of its E3 ubiquitin ligase activity and DNA interstrand crosslink repair.
External links	Nature / PubMed:31666700 / PubMed Central
Methods	EM (single particle)
Resolution	4.2 - 4.9 Å
Structure data	10290 6sri EMDB-10290: Structure of Fanconi anaemia core complex (consensus map) PDB-6sri: Structure of the Fanconi anaemia core complex Method: EM (single particle) / Resolution: 4.2 Å EMDB-10291: Structure of the Fanconi Anaemia core complex (focussed map for top region) Method: EM (single particle) / Resolution: 4.5 Å EMDB-10292: Structure of the Fanconi Anaemia core complex (focussed map for middle region) Method: EM (single particle) / Resolution: 4.4 Å EMDB-10293: Structure of the Fanconi Anaemia core complex (focussed map for base region) Method: EM (single particle) / Resolution: 4.9 Å 10294 6srs EMDB-10294, PDB-6srs: Structure of the Fanconi anaemia core subcomplex Method: EM (single particle) / Resolution: 4.6 Å
Source	gallus gallus (chicken)
Keywords	LIGASE / Fanconi Anaemia core complex; E3 ligase; DNA repair