Proteasome articles from across Nature Portfolio

Precise protease positioning and gating of the proteasome core require the ordered assembly of 28 subunits. Cryo-EM structures of seven intermediates visualize five dedicated chaperones and three propeptides mediating step-by-step assembly of the human 20S proteasome.

To prevent promiscuous protein degradation, proteasomes are initially assembled as inactive complexes. Their activation is autocatalytic and coupled to assembly. Here the authors uncover key aspects of the autocatalytic activation mechanism.

Xenopus egg extracts constitute a cell-like system for studying biochemical reactions. Here Chen and co-workers show that extract protein synthesis and degradation are differently affected by cytoplasmic concentration and viscosity.

In the kidney, maintaining permeability of the filtration barrier is critical. Here, Sachs W. et al show that homeostasis of podocytes and glomerular endothelial cells relies on differing proteasome constitutions which orchestrate endocytic activity in addition to protein degradation.

SAP05, a secreted effector of the obligate parasitic bacteria phytoplasma, bridges host SPL and GATA transcription factors (TFs) to the 26 S proteasome subunit RPN10 for ubiquitination-independent degradation. Here, the authors report the details on how SAP05 interacts with SPL5, GATA18 and RPN10.

Do proteasomes catalyze peptide splicing? Here, the authors develop and apply a method to identify spliced peptides produced from entire proteins, confirm that proteasomes produce a sizeable variety of cis-spliced peptides with well-defined characteristics, and show that non-spliced and spliced peptides are concentrated in hotspots.

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

mTOR inhibition by deprivation of the amino acids Tyr, Trp and Phe promotes the translocation of the 26S proteasome from the nucleus to the cytosol, which is required for stress tolerance and cell survival.

Cold temperature prolongs lifespan in nematodes by inducing ubiquitin-independent proteasome activity, which prevents protein aggregation and neuronal degeneration. The pathway is conserved in humans.

Moderately cold temperatures trigger the removal of aggregation-prone proteins in the invertebrate model Caenorhabditis elegans and cultured human cells, preventing the accumulation of pathological aggregates linked with age-related neurodegenerative disorders such as amyotrophic lateral sclerosis and Huntington’s disease.