8tm4 | pdb_00008tm4

Human pre 13S proteasome assembly intermediate

spinqualitylabelsall models 8tm4, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8tm4 is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PSA2_HUMAN The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. Publication Abstract from PubMed 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 alpha-ring intermediate subcomplex that is stabilized by PAC1-4, which transitions to beta-ring assembly upon dissociation of PAC3/PAC4 and rearrangement of the PAC1 N-terminal tail. Completion of the beta-ring and dimerization of half-proteasomes repositions critical lysine K33 to trigger cleavage of the beta 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. Structural basis of human 20S proteasome biogenesis.,Zhang H, Zhou C, Mohammad Z, Zhao J Nat Commun. 2024 Sep 18;15(1):8184. doi: 10.1038/s41467-024-52513-0. PMID:39294158 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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