Methods to direct the degradation of protein targets with proximity-inducing molecules that
coopt the cellular degradation machinery are advancing in leaps and bounds, and diverse
modalities are emerging. The most used and well-studied approach is to hijack E3 ligases of
the ubiquitin–proteasome system. E3 ligases use specific molecular recognition to
determine which proteins in the cell are ubiquitinated and degraded. This review focuses on
the structural determinants of E3 ligase recruitment of natural substrates and neo-substrates …