An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence.
Zinc finger transcription factor Zfp57 recognizes the methylated CpG within the TGCCGC element. We determined the structure of the DNA-binding domain of Zfp57, consisting of two adjacent zinc fingers, in complex with fully methylated DNA at 1.0 Å resolution. The first zinc finger contacts the 5' half (TGC), and the second recognizes the 3' half (CGC) of the recognition sequence. Zfp57 recognizes the two 5-methylcytosines (5mCs) asymmetrically: One involves hydrophobic interactions with Arg178, which also interacts with the neighboring 3' guanine and forms a 5mC-Arg-G interaction, while the other involves a layer of ordered water molecules. Two point mutations in patients with transient neonatal diabetes abolish DNA-binding activity. Zfp57 has reduced binding affinity for unmodified DNA and the oxidative products of 5mC.
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Yiwei
Y
Liu
Hidehiro
H
Toh
Hiroyuki
H
Sasaki
Xing
X
Zhang
Xiaodong
X
Cheng
D000595:Amino Acid Sequence; D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment
D008024:Ligands; D012097:Repressor Proteins; C501529:Zfp-57 protein, mouse