Bidirectional control of a metabolic transition by the GID ubiquitin ligase

GID/CTLH has been implicated in a variety of processes, including metabolic regulation, cell proliferation, embryonic development and cell differentiation. However, our understanding of substrate recognition by GID/CTLH remains incomplete.

Here, we characterize the regulation, specificity and functions of the putative substrate receptor Gid11 in budding yeast. We find that upon its expression during the switch of carbon source from glucose to ethanol, Gid11 associates with the core GID complex, likely forming a large ring assembly. Through systematic mutagenesis, we identify a negatively charged pocket on Gid11 that binds substrates carrying N-terminal degrons starting with threonine and define the Thr/N-degron motif.