Ubiquitin ligases articles from across Nature Portfolio

Gene variants can affect folding and stability of the encoded protein. Here, the authors apply deep mutational scanning to provide genotype-phenotype information for 99% of the possible PRKN variants and reveal mechanistic details on how some variants cause loss-of-function and Parkinsons disease.

The importance of the SEL1L-HRD1 interaction in vivo was unclear. Here, authors reported that SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex by recruiting the E2 enzyme UBE2J1 and DERLIN to HRD1.

Here, upon obtaining cryo-EM structures of CRL3^KBTBD2 in seven states, the authors propose a model for the activation cycle of CRL3 ligases, including assembly, substrate recruitment, (de)neddylation and CAND1-mediated substrate receptor exchange.

The authors define a NEDD8-activated cullin-RING E3 poly-ubiquitylation mechanism using chemistry, cryo-EM and rapid kinetics. Near-perfect catalytic efficiency is achieved by an E2 ‘synergy loop’ connecting to the E3, donor and acceptor ubiquitins.

Thomas Arnesen and colleagues discuss an emerging major role of one of the most common protein modifications, N-terminal acetylation, in shielding the proteome from degradation.

Harmful activity of the DNA sensor cGAS in the nucleus is suppressed by a dedicated ubiquitylation complex.

Scott et al. describe a mechanism based on C-degron mimicry by which an E3 ubiquitin ligase discriminates bona fide substrates from non-physiological substrates.