Solution structure of a zinc-finger domain that binds to poly-ADP-ribose.
Poly-ADP-ribosylation is a unique post-translational modification that controls various nuclear events such as repair of DNA single-strand breaks. Recently, the protein containing the poly-ADP-ribose (pADPr)-binding zinc-finger (PBZ) domain was shown to be a novel AP endonuclease and involved in a cell cycle checkpoint. Here, we determined the three-dimensional structure of the PBZ domain from Drosophila melanogaster CG1218-PA using NMR spectroscopy. The domain folds into a C2H2-type zinc-finger structure in an S configuration, containing a characteristic loop between the zinc-coordinating cysteine and histidine residues. This is distinct from the structure of other C2H2-type zinc fingers. NMR signal changes that occur when pADPr binds to the PBZ domains from CG1218-PA and human checkpoint with FHA (forkhead-associated) and ring finger (CHFR) and mutagenesis suggest that a surface relatively well conserved among PBZ domains may serve as a major interface with pADPr.
Isogai
Shin
S
Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto-Daigaku Katsura, Kyoto 615-8510, Japan.
Kanno
Shin-Ichiro
S
Ariyoshi
Mariko
M
Tochio
Hidehito
H
Ito
Yutaka
Y
Yasui
Akira
A
Shirakawa
Masahiro
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers / Q000235:genetics
C551444:CG1218 protein, Drosophila; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011064:Poly Adenosine Diphosphate Ribose; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases