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TitleStructural basis of human 20S proteasome biogenesis.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 8184, Year 2024
Publish dateSep 18, 2024
AuthorsHanxiao Zhang / Chenyu Zhou / Zarith Mohammad / Jianhua Zhao /
PubMed AbstractNew proteasomes are produced to accommodate increases in cellular catabolic demand and prevent the accumulation of cytotoxic proteins. Formation of the proteasomal 20S core complex relies on the ...New proteasomes are produced to accommodate increases in cellular catabolic demand and prevent the accumulation of cytotoxic proteins. Formation of the proteasomal 20S core complex relies on the function of the five chaperones PAC1-4 and POMP. Here, to understand how these chaperones facilitate proteasome assembly, we tagged the endogenous chaperones using CRISPR/Cas gene editing and examined the chaperone-bound complexes by cryo-EM. We observe an early α-ring intermediate subcomplex that is stabilized by PAC1-4, which transitions to β-ring assembly upon dissociation of PAC3/PAC4 and rearrangement of the PAC1 N-terminal tail. Completion of the β-ring and dimerization of half-proteasomes repositions critical lysine K33 to trigger cleavage of the β pro-peptides, leading to the concerted dissociation of POMP and PAC1/PAC2 to yield mature 20S proteasomes. This study reveals structural insights into critical points along the assembly pathway of the human proteasome and provides a molecular blueprint for 20S biogenesis.
External linksNat Commun / PubMed:39294158 / PubMed Central
MethodsEM (single particle)
Resolution2.8 - 3.0 Å
Structure data

EMDB-41377, PDB-8tm3:
Human proteasome alpha ring assembly intermediate
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-41378, PDB-8tm4:
Human pre 13S proteasome assembly intermediate
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-41379, PDB-8tm5:
Human mixed 13S proteasome assembly intermediate
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-41380, PDB-8tm6:
Human premature 20S proteasome assembly intermediate
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-41381: Premature human 20S proteasome assembly intermediate 37C
Method: EM (single particle) / Resolution: 2.8 Å

Source
  • homo sapiens (human)
KeywordsHYDROLASE / proteasome / proteasome assembly / PAC3 / PAC4 / POMP / beta ring assembly / 20S / proteasome core particle

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