Structures of chaperone-associated assembly intermediates reveal coordinated mechanisms of proteasome biogenesis

Nat Struct Mol Biol. 2021 Apr 12. doi: 10.1038/s41594-021-00583-9. Online ahead of print.ABSTRACTThe proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an α7β7β7α7 configuration. CP biogenesis proceeds through an ordered multistep pathway requiring five chaperones, Pba1-4 and Ump1. Using Saccharomyces cerevisiae, we report high-resolution structures of CP assembly intermediates by cryogenic-electron microscopy. The first structure corresponds to the 13S particle, which consists of a complete α-ring, partial β-ring (β2-4), Ump1 and Pba1/2. The second structure contains two additional subunits (β5-6) and represents a later pre-15S intermediate. These structures reveal the architecture and positions of Ump1 and β2/β5 propeptides, with important implications for their functions. Unexpectedly, Pba1's N terminus extends through an open CP pore, accessing the CP interior to contact Ump1 and the β5 propeptide. These results reveal how the coordinated activity of Ump1, Pba1 and the active site propeptides orchestrate key aspects of CP assembly.PMID:33846632 | DOI:10.1038/s41594-021-00583-9

Source: Mol Biol Cell - April 13, 2021 Category: Molecular Biology Authors: Helena M Schnell Richard M Walsh Shaun Rawson Mandeep Kaur Meera K Bhanu Geng Tian Miguel A Prado Angel Guerra-Moreno Joao A Paulo Steven P Gygi Jeroen Roelofs Daniel Finley John Hanna Source Type: research