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TitleStructural roles of Ump1 and β-subunit propeptides in proteasome biogenesis.
Journal, issue, pagesLife Sci Alliance, Vol. 7, Issue 11, Year 2024
Publish dateSep 11, 2024
AuthorsEric Mark / Paula C Ramos / Fleur Kayser / Jörg Höckendorff / R Jürgen Dohmen / Petra Wendler /
PubMed AbstractThe yeast (β4-S142F) mutant accumulates late 20S proteasome core particle precursor complexes (late-PCs). We report a 2.1 Å cryo-EM structure of this intermediate with full-length Ump1 trapped ...The yeast (β4-S142F) mutant accumulates late 20S proteasome core particle precursor complexes (late-PCs). We report a 2.1 Å cryo-EM structure of this intermediate with full-length Ump1 trapped inside, and Pba1-Pba2 attached to the α-ring surfaces. The structure discloses intimate interactions of Ump1 with β2- and β5-propeptides, which together fill most of the antechambers between the α- and β-rings. The β5-propeptide is unprocessed and separates Ump1 from β6 and β7. The β2-propeptide is disconnected from the subunit by autocatalytic processing and localizes between Ump1 and β3. A comparison of different proteasome maturation states reveals that maturation goes along with global conformational changes in the rings, initiated by structuring of the proteolytic sites and their autocatalytic activation. In the strain, β2 is activated first enabling processing of β1-, β6-, and β7-propeptides. Subsequent maturation of β5 and β1 precedes degradation of Ump1, tightening of the complex, and finally release of Pba1-Pba2.
External linksLife Sci Alliance / PubMed:39260885 / PubMed Central
MethodsEM (single particle)
Resolution2.02 - 2.69 Å
Structure data

EMDB-19523, PDB-8rvl:
Proteasomal late precursor complex from pre1-1
Method: EM (single particle) / Resolution: 2.14 Å

EMDB-19527, PDB-8rvo:
Proteasomal late precursor complex from pre1-1, state 1
Method: EM (single particle) / Resolution: 2.69 Å

EMDB-19528, PDB-8rvp:
Proteasomal late precursor complex from pre1-1, state 2
Method: EM (single particle) / Resolution: 2.28 Å

EMDB-19529, PDB-8rvq:
20S proteasome from pre1-1
Method: EM (single particle) / Resolution: 2.02 Å

EMDB-51221, PDB-9gbk:
Blm10-20S proteasome complex from pre1-1
Method: EM (single particle) / Resolution: 2.39 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsHYDROLASE / proteasome biogenesis / Ump1 / pre1-1 / cryo-EM / propertied maturation

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