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TitleStructures of chaperone-associated assembly intermediates reveal coordinated mechanisms of proteasome biogenesis.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 5, Page 418-425, Year 2021
Publish dateApr 12, 2021
AuthorsHelena 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 /
PubMed AbstractThe proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an αββα configuration. CP biogenesis proceeds ...The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an αββα 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.
External linksNat Struct Mol Biol / PubMed:33846632 / PubMed Central
MethodsEM (single particle)
Resolution2.74 - 3.61 Å
Structure data

EMDB-23502, PDB-7ls5:
Cryo-EM structure of the Pre3-1 20S proteasome core particle
Method: EM (single particle) / Resolution: 2.74 Å

EMDB-23503, PDB-7ls6:
Cryo-EM structure of Pre-15S proteasome core particle assembly intermediate purified from Pre3-1 proteasome mutant (G34D)
Method: EM (single particle) / Resolution: 3.17 Å

EMDB-23508, PDB-7lsx:
Cryo-EM structure of 13S proteasome core particle assembly intermediate purified from Pre3-1 proteasome mutant (G34D)
Method: EM (single particle) / Resolution: 3.61 Å

Source
  • Saccharomyces cerevisiae S288C (yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
KeywordsHYDROLASE / core particle / complex / assembly intermediate

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