3WWQ

Crystal structure of FAAP20 UBZ domain in complex with Lys63-linked diubiquitin

Summary for 3WWQ

• Entry DOI: 10.2210/pdb3wwq/pdb
• Descriptor: Ubiquitin, Fanconi anemia-associated protein of 20 kDa, ZINC ION, ... (5 entities in total)
• Functional Keywords: protein complex, dna repair, protein binding-metal binding protein complex, protein binding/metal binding protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm : P0CG50 P0CG50; Nucleus: Q6NZ36
• Total number of polymer chains: 12
• Total formula weight: 88846.70

Authors

Sato, Y.,Fukai, S. (deposition date: 2014-06-23, release date: 2015-05-13, Last modification date: 2023-11-08)

Primary citation

Toma, A.,Takahashi, T.S.,Sato, Y.,Yamagata, A.,Goto-Ito, S.,Nakada, S.,Fukuto, A.,Horikoshi, Y.,Tashiro, S.,Fukai, S.
Structural Basis for Ubiquitin Recognition by Ubiquitin-Binding Zinc Finger of FAAP20
Plos One, 10:e0120887-e0120887, 2015

PubMed Abstract: Several ubiquitin-binding zinc fingers (UBZs) have been reported to preferentially bind K63-linked ubiquitin chains. In particular, the UBZ domain of FAAP20 (FAAP20-UBZ), a member of the Fanconi anemia core complex, seems to recognize K63-linked ubiquitin chains, in order to recruit the complex to DNA interstrand crosslinks and mediate DNA repair. By contrast, it is reported that the attachment of a single ubiquitin to Rev1, a translesion DNA polymerase, increases binding of Rev1 to FAAP20. To clarify the specificity of FAAP20-UBZ, we determined the crystal structure of FAAP20-UBZ in complex with K63-linked diubiquitin at 1.9 Å resolution. In this structure, FAAP20-UBZ interacts only with one of the two ubiquitin moieties. Consistently, binding assays using surface plasmon resonance spectrometry showed that FAAP20-UBZ binds ubiquitin and M1-, K48- and K63-linked diubiquitin chains with similar affinities. Residues in the vicinity of Ala168 within the α-helix and the C-terminal Trp180 interact with the canonical Ile44-centered hydrophobic patch of ubiquitin. Asp164 within the α-helix and the C-terminal loop mediate a hydrogen bond network, which reinforces ubiquitin-binding of FAAP20-UBZ. Mutations of the ubiquitin-interacting residues disrupted binding to ubiquitin in vitro and abolished the accumulation of FAAP20 to DNA damage sites in vivo. Finally, structural comparison among FAAP20-UBZ, WRNIP1-UBZ and RAD18-UBZ revealed distinct modes of ubiquitin binding. UBZ family proteins could be divided into at least three classes, according to their ubiquitin-binding modes.

PubMed: 25799058
DOI: 10.1371/journal.pone.0120887

Experimental method

X-RAY DIFFRACTION (1.9 Å)