Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor

• Published in: Nature structural & molecular biology Vol. 15; no. 1; pp. 109 - 111
• Main Authors: Mer, Georges, Lee, Joseph, Thompson, James R, Botuyan, Maria Victoria
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-01-2008; Nature Publishing Group
• Subjects: Binding Sites; Biochemistry; Biological Microscopy; Biomedical and Life Sciences; brief-communication; Calorimetry; Crystallography; Genetic aspects; Histones; Histones - chemistry; Histones - metabolism; Humans; Jumonji Domain-Containing Histone Demethylases; Life Sciences; Membrane Biology; Methylation; Methyltransferases; Models, Molecular; Molecular biology; Molecular structure; Mutagenesis, Site-Directed; Mutation; Oxidoreductases, N-Demethylating - chemistry; Oxidoreductases, N-Demethylating - genetics; Oxidoreductases, N-Demethylating - metabolism; Peptides; Physiological aspects; Protein Conformation; Protein Structure; Sensitivity and Specificity; Structure; United States
• ISSN: 1545-9993; 1545-9985
• DOI: 10.1038/nsmb1326

The lysine demethylase JMJD2A has the unique property of binding trimethylated peptides from two different histone sequences (H3K4me3 and H4K20me3) through its tudor domains. Here we show using X-ray crystallography and calorimetry that H3K4me3 and H4K20me3, which are recognized with similar affinities by JMJD2A, adopt radically different binding modes, to the extent that we were able to design single point mutations in JMJD2A that inhibited the recognition of H3K4me3 but not H4K20me3 and vice versa.