Ubiquitin and Ubl signaling

The first structure of fully active HOIP of the RBR family of RING-type E3 ligases in its transfer complex with an E2~ubiquitin conjugate provides insights into its mechanism of action, including the ideal alignment of the E2 and E3 catalytic centres for ubiquitin transfer and the allosteric regulation of the RBR family.

The authors define molecular mechanisms by which distinct domains of the ubiquitin editing enzyme A20 contribute to the regulation of inflammation and cell death.

The PINK1 ubiquitin kinase is shown to recruit the two autophagy receptors NDP52 and OPTN to mitochondria to activate mitophagy directly, independently of the ubiquitin ligase parkin; once recruited to mitochondria, NDP52 and OPTN recruit autophagy initiation components, and parkin may amplify the phospho-ubiquitin signal generated by PINK1, resulting in robust autophagy induction.