9d0t
From Proteopedia
Core particle assembly intermediate 1 purified from Saccharomyces cerevisiae
Structural highlights
FunctionPSB3_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. This subunit may participate in the trypsin-like activity of the enzyme complex. Publication Abstract from PubMedProteasomes are formed by chaperone-assisted assembly of core particles (CPs) and regulatory particles (RPs). The CP chaperone dimer Pba1/Pba2 binds early to proteasome subunits, and is thought to be replaced by Blm10 to form Blm10:CP, which promotes ATP-independent degradation of disordered proteins. Here, we present evidence of distinct parallel assembly pathways for CP by solving five cryo-EM structures including a Blm10:13S pre-assembly intermediate. Our data conflict with the current model of Blm10 and Pba1/Pba2 sequential activity in a single assembly pathway, as we find their CP binding is mutually exclusive and both are present on early and late assembly intermediates. CP affinity for Pba1/Pba2 is reduced during maturation, promoting Pba1/Pba2 release. We find Blm10 undergoes no such affinity switch, suggesting this pathway predominantly yields mature Blm10-bound CP. Altogether, our findings conflict with the current paradigm of sequential CP binding to instead indicate parallel assembly pathways by Pba1/Pba2 and Blm10. Structure of Blm10:13S proteasome intermediate reveals parallel assembly pathways for the proteasome core particle.,Kaur M, Chen X, Lee SY, Weaver TM, Freudenthal BD, Walters KJ, Roelofs J bioRxiv [Preprint]. 2024 Nov 5:2024.11.04.621988. doi: 10.1101/2024.11.04.621988. PMID:39574619[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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