8u6y
From Proteopedia
Preholo-Proteasome from Beta 3 D205 deletion
Structural highlights
FunctionPSA3_YEAST The proteasome degrades poly-ubiquitinated proteins in the cytoplasm and in the nucleus. It is essential for the regulated turnover of proteins and for the removal of misfolded proteins. The proteasome is a multicatalytic proteinase complex that 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. It has an ATP-dependent proteolytic activity. Publication Abstract from PubMedMany large molecular machines are too elaborate to assemble spontaneously and are built through ordered pathways orchestrated by dedicated chaperones. During assembly of the core particle (CP) of the proteasome, where protein degradation occurs, its six active sites are simultaneously activated via cleavage of N-terminal propeptides. Such activation is autocatalytic and coupled to fusion of two half-CP intermediates, which protects cells by preventing activation until enclosure of the active sites within the CP interior. Here we uncover key mechanistic aspects of autocatalytic activation, which proceeds through alignment of the beta5 and beta2 catalytic triad residues, respectively, with these triads being misaligned before fusion. This mechanism contrasts with most other zymogens, in which catalytic centers are preformed. Our data also clarify the mechanism by which individual subunits can be added in a precise, temporally ordered manner. This work informs two decades-old mysteries in the proteasome field, with broader implications for protease biology and multisubunit complex assembly. Mechanism of autocatalytic activation during proteasome assembly.,Velez B, Walsh RM Jr, Rawson S, Razi A, Adams L, Perez EF, Jiao F, Blickling M, Rajakumar T, Fung D, Huang L, Hanna J Nat Struct Mol Biol. 2024 Aug;31(8):1167-1175. doi: 10.1038/s41594-024-01262-1. , Epub 2024 Apr 10. PMID:38600323[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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