Identification of Methyllysine Peptides Binding to Chromobox Protein Homolog 6 Chromodomain in the Human Proteome

• Published in: Molecular & cellular proteomics Vol. 12; no. 10; pp. 2750 - 2760
• Main Authors: Li, Nan, Stein, Richard S.L., He, Wei, Komives, Elizabeth, Wang, Wei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2013; The American Society for Biochemistry and Molecular Biology
• Subjects: Chromosomal Proteins, Non-Histone - chemistry; Chromosomal Proteins, Non-Histone - metabolism; Humans; Lysine - metabolism; Methylation; Models, Molecular; Peptides - metabolism; Protein Processing, Post-Translational; Protein Structure, Tertiary; Proteome
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.O112.025015

Methylation is one of the important post-translational modifications that play critical roles in regulating protein functions. Proteomic identification of this post-translational modification and understanding how it affects protein activity remain great challenges. We tackled this problem from the aspect of methylation mediating protein–protein interaction. Using the chromodomain of human chromobox protein homolog 6 as a model system, we developed a systematic approach that integrates structure modeling, bioinformatics analysis, and peptide microarray experiments to identify lysine residues that are methylated and recognized by the chromodomain in the human proteome. Given the important role of chromobox protein homolog 6 as a reader of histone modifications, it was interesting to find that the majority of its interacting partners identified via this approach function in chromatin remodeling and transcriptional regulation. Our study not only illustrates a novel angle for identifying methyllysines on a proteome-wide scale and elucidating their potential roles in regulating protein function, but also suggests possible strategies for engineering the chromodomain–peptide interface to enhance the recognition of and manipulate the signal transduction mediated by such interactions.