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From Proteopedia
Human proteasome 20S core particle
Structural highlights
FunctionPSA2_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 PubMedDedicated assembly factors orchestrate the stepwise production of many molecular machines, including the 28-subunit proteasome core particle (CP) that mediates protein degradation. Here we report cryo-electron microscopy reconstructions of seven recombinant human subcomplexes that visualize all five chaperones and the three active site propeptides across a wide swath of the assembly pathway. Comparison of these chaperone-bound intermediates and a matching mature CP reveals molecular mechanisms determining the order of successive subunit additions, as well as how proteasome subcomplexes and assembly factors structurally adapt upon progressive subunit incorporation to stabilize intermediates, facilitate the formation of subsequent intermediates and ultimately rearrange to coordinate proteolytic activation with gated access to active sites. This work establishes a methodologic approach for structural analysis of multiprotein complex assembly intermediates, illuminates specific functions of assembly factors and reveals conceptual principles underlying human proteasome biogenesis, thus providing an explanation for many previous biochemical and genetic observations. Visualizing chaperone-mediated multistep assembly of the human 20S proteasome.,Adolf F, Du J, Goodall EA, Walsh RM Jr, Rawson S, von Gronau S, Harper JW, Hanna J, Schulman BA Nat Struct Mol Biol. 2024 Aug;31(8):1176-1188. doi: 10.1038/s41594-024-01268-9. , Epub 2024 Apr 10. PMID:38600324[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found References
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Categories: Homo sapiens | Large Structures | Adolf F | Du J | Goodall EA | Hanna JW | Harper JW | Rawson SD | Schulman BA | Walsh Jr RM