title: Identification of methyllysine peptides binding to chromobox protein homolog 6 chromodomain in the human proteome.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, 9500 Gilman Drive, University of California, San Diego, La Jolla, California 92093-0359;
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Richard S L
authors.initials: RS
authors.lastname: Stein
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Komives
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D020543:Proteome
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D010455:Peptides; D020543:Proteome; D008239:Lysine