2XP0

C-terminal cysteine-rich domain of human CHFR

Summary for 2XP0

• Entry DOI: 10.2210/pdb2xp0/pdb
• Related: 1LGP 1LGQ 2XOC 2XOY 2XOZ
• Descriptor: E3 UBIQUITIN-PROTEIN LIGASE CHFR, ZINC ION (3 entities in total)
• Functional Keywords: ligase, zinc-binding, pbz, mitosis, antephase checkpoint
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus, PML body: Q96EP1
• Total number of polymer chains: 2
• Total formula weight: 62127.53

Authors

Oberoi, J.,Bayliss, R. (deposition date: 2010-08-24, release date: 2010-09-29, Last modification date: 2024-10-23)

Primary citation

Oberoi, J.,Richards, M.W.,Crumpler, S.,Brown, N.,Blagg, J.,Bayliss, R.
Structural Basis of Poly(Adp-Ribose) Recognition by the Multizinc Binding Domain of Checkpoint with Forkhead-Associated and Ring Domains (Chfr).
J.Biol.Chem., 285:39348-, 2010

PubMed Abstract: Cellular stress in early mitosis activates the antephase checkpoint, resulting in the decondensation of chromosomes and delayed mitotic progression. Checkpoint with forkhead-associated and RING domains (CHFR) is central to this checkpoint, and its activity is ablated in many tumors and cancer cell lines through promoter hypermethylation or mutation. The interaction between the PAR-binding zinc finger (PBZ) of CHFR and poly(ADP-ribose) (PAR) is crucial for a functional antephase checkpoint. We determined the crystal structure of the cysteine-rich region of human CHFR (amino acids 425-664) to 1.9 Å resolution, which revealed a multizinc binding domain of elaborate topology within which the PBZ is embedded. The PBZ of CHFR closely resembles the analogous motifs from aprataxin-like factor and CG1218-PA, which lie within unstructured regions of their respective proteins. Based on co-crystal structures of CHFR bound to several different PAR-like ligands (adenosine 5'-diphosphoribose, adenosine monophosphate, and P(1)P(2)-diadenosine 5'-pyrophosphate), we made a model of the CHFR-PAR interaction, which we validated using site-specific mutagenesis and surface plasmon resonance. The PBZ motif of CHFR recognizes two adenine-containing subunits of PAR and the phosphate backbone that connects them. More generally, PBZ motifs may recognize different numbers of PAR subunits as required to carry out their functions.

PubMed: 20880844
DOI: 10.1074/JBC.M110.159855

Experimental method

X-RAY DIFFRACTION (1.978 Å)