The Tudor tandem of 53BP1: a new structural motif involved in DNA and RG-rich peptide binding.
53BP1 is a key transducer of the DNA damage checkpoint signal, which is required for phosphorylation of a subset of ATM substrates and p53 accumulation. After cell irradiation, the 53BP1 N-terminal region is phosphorylated. Its two C-terminal BRCT motifs interact with p53. Its central region is required and sufficient for 53BP1 foci formation at DNA strand breaks and for 53BP1 binding to the kinetochore. It contains an RG-rich segment and interacts with DNA in vitro. Here we show that the major globular domain of the 53BP1 central region adopts a new structural motif composed of two tightly packed Tudor domains and a C-terminal alpha helix. A unique surface essentially located on the first Tudor domain is involved in the binding to 53BP1 RG-rich sequence and to DNA, suggesting that the Tudor tandem can act as an adaptor mediating intramolecular as well as intermolecular protein-protein interactions and protein-nucleic acid associations.
Charier
Gaëlle
G
Département d'Ingénierie et d'Etudes des Protéines, 91191 Gif-sur-Yvette, France.
Couprie
Joël
J
Alpha-Bazin
Béatrice
B
Meyer
Vincent
V
Quéméneur
Eric
E
Guérois
Raphaël
R
Callebaut
Isabelle
I
Gilquin
Bernard
B
Zinn-Justin
Sophie
S
D000595:Amino Acid Sequence; D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D000071857:Tumor Suppressor p53-Binding Protein 1
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010455:Peptides; D010750:Phosphoproteins; C498301:TP53BP1 protein, human; C498302:Trp53bp1 protein, mouse; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA