7AY1
Cryo-EM structure of USP1-UAF1 bound to mono-ubiquitinated FANCD2, and FANCI
Summary for 7AY1
| Entry DOI | 10.2210/pdb7ay1/pdb |
| EMDB information | 11934 |
| Descriptor | Fanconi anemia group I protein, Fanconi anemia group D2 protein, Ubiquitin-60S ribosomal protein L40, ... (7 entities in total) |
| Functional Keywords | deubiquitination, specificity, dna repair, fanconi anemia, hydrolase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 7 |
| Total formula weight | 501070.06 |
| Authors | Rennie, M.L.,Arkinson, C.,Walden, H. (deposition date: 2020-11-10, release date: 2021-03-24, Last modification date: 2024-10-23) |
| Primary citation | Rennie, M.L.,Arkinson, C.,Chaugule, V.K.,Toth, R.,Walden, H. Structural basis of FANCD2 deubiquitination by USP1-UAF1. Nat.Struct.Mol.Biol., 28:356-364, 2021 Cited by PubMed Abstract: Ubiquitin-specific protease 1 (USP1) acts together with the cofactor UAF1 during DNA repair processes to specifically remove monoubiquitin signals. One substrate of the USP1-UAF1 complex is the monoubiquitinated FANCI-FANCD2 heterodimer, which is involved in the repair of DNA interstrand crosslinks via the Fanconi anemia pathway. Here we determine structures of human USP1-UAF1 with and without ubiquitin and bound to monoubiquitinated FANCI-FANCD2. The crystal structures of USP1-UAF1 reveal plasticity in USP1 and key differences to USP12-UAF1 and USP46-UAF1, two related proteases. A cryo-EM reconstruction of USP1-UAF1 in complex with monoubiquitinated FANCI-FANCD2 highlights a highly orchestrated deubiquitination process, with USP1-UAF1 driving conformational changes in the substrate. An extensive interface between UAF1 and FANCI, confirmed by mutagenesis and biochemical assays, provides a molecular explanation for the requirement of both proteins, despite neither being directly involved in catalysis. Overall, our data provide molecular details of USP1-UAF1 regulation and substrate recognition. PubMed: 33795880DOI: 10.1038/s41594-021-00576-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.7 Å) |
Structure validation
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