Uncovering post-translational modification-associated protein-protein interactions

Abstract

In living systems, the chemical space and functional repertoire of proteins are dramatically expanded through the post-translational modification (PTM) of various amino acid residues. These modifications frequently trigger unique protein-protein interactions (PPIs) - for example with reader proteins that directly bind the modified amino acid residue - which leads to downstream functional outcomes. The modification of a protein can also perturb its PPI network indirectly, for example, through altering its conformation or subcellular localization. Uncovering the network of unique PTM-triggered PPIs is essential to fully understand the roles of an ever-expanding list of PTMs in our biology. In this review, we discuss established strategies and current challenges associated with this endeavor.

Figure 1.

PTMs can lead to novel PPIs either directly or indirectly

Figure 2.

A-C show different approaches to identify novel PTM-associated PPIs. D) Structures of ncAAs with photo-crosslinkers frequently used to capture PPIs. E) Novel lysine-derived ncAAs, harboring a diazirine group, which can be incorporated into proteins and used to capture interactors that bind this residue