Climbing into their Skin to Understand Contextual Protein-Protein Associations and Localizations: Functional Investigations in Transgenic Live Model Organisms

Borrowing some quotes from Harper Lee's novel "To Kill A Mockingbird" to help frame our manuscript, we discuss methods to profile local proteomes. We initially focus on chemical biology regimens that function in live organisms and use reactive biotin species for this purpose. We then consider ways to add new dimensions to these experimental regimens, principally by releasing less reactive (i. e., more selective) (preter)natural electrophiles. Although electrophile release methods may have lower resolution and label fewer proteins than biotinylation methods, their ability to probe simultaneously protein function and locale raises new and interesting possibilities for the field.|What Stirs Beneath. Understanding protein-specific interactomes, or localization, is crucial for decoding protein function. New biotinylation methods can do just that even in live organisms. However, these methods have some limitations as they are intrinsically unable to directly probe function. Here new methods that can investigate locale-specific reactivity, are discussed, opening routes to locale-specific perturbation of function. image