Research Regulation of the ubiquitin ligase Ubr1 by the intrinsically disordered Roq1
how the speed and specificity of protein degradation is controlled
Cells often encounter stressful conditions that damage their proteins. To prevent an accumulation of damaged and potentially harmful proteins, cells activate quality control mechanisms. One such mechanism in budding yeast is the reprograming of the ubiquitin ligase Ubr1 by the small stress-responsive protein Roq1. Interestingly, Roq1 increases Ubr1’s ability to recognize and destroy damaged proteins but, at the same time, stops Ubr1 from attacking certain other proteins that cells want to keep during stress. In their new study, the Schuck lab investigated the biochemical mechanism by which Roq1 reprograms Ubr1. In particular, they identified cooperating structural features of Roq1 that help Ubr1 to destroy damaged proteins. These insights may inspire the design of artificial modulators of protein degradation to help cells - including human cells - to get rid of dangerous and disease-causing proteins.
