Functional Aspects

In general, proteins associated with signals from acetylated and methylated proteins can be broadly classified into the writer-reader-eraser model. In this scheme, enzymes mediating the addition and removal of the acetyl or methyl groups are “writers” and “erasers" Proteins interacting with the post-translationally modified proteins are “readers” [2, 14]. The primary “readers” of methylation and acetylation marks are Tudor domain- and bromodomain-containing proteins [15, 16]. Acetyl and methyl groups do not themselves confer charge but can modulate charge by removing the positive charge from the e-amino group oflysine. Addition of these groups also introduces steric hindrance, with the net result of modulating protein-protein and protein-nucleic acid interactions. The biological significance of both protein acetylation and methylation is underlined by the development of specific inhibitors against methyltransferase (lysine and arginine) and deacety- lases as “druggable” therapeutic targets for clinical application [17, 18]. Beyond clinical application, these inhibitors also provide biochemical reagents for probing of functional analysis [19]. Acetylation and methylation have combinatorial activity with other PTMs; thus a number of proteoforms/protein can exist. The term proteoform describes biological variability and complexity at the level of protein primary structure, including isoform and PTM variants for the products of a single gene [20].

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