7qo5 | pdb_00007qo5

26S proteasome Rpt1-RK -Ubp6-UbVS complex in the si state

spinqualitylabelsall models 7qo5, resolution 6.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7qo5 is a 12 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, ATP, GLZ, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PSB2_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 PubMed The proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by deubiquitinating enzyme Ubp6. The proteasome activates Ubp6, whereas Ubp6 inhibits the proteasome through deubiquitination and a noncatalytic effect. Here, we report cryo-EM structures of the proteasome bound to Ubp6, based on which we identify mutants in Ubp6 and proteasome subunit Rpt1 that abrogate Ubp6 activation. The Ubp6 mutations define a conserved region that we term the ILR element. The ILR is found within the BL1 loop, which obstructs the catalytic groove in free Ubp6. Rpt1-ILR interaction opens the groove by rearranging not only BL1 but also a previously undescribed network of three interconnected active-site-blocking loops. Ubp6 activation and noncatalytic proteasome inhibition are linked in that they are eliminated by the same mutations. Ubp6 and ubiquitin together drive proteasomes into a unique conformation associated with proteasome inhibition. Thus, a multicomponent allosteric switch exerts simultaneous control over both Ubp6 and the proteasome. Allosteric control of Ubp6 and the proteasome via a bidirectional switch.,Hung KYS, Klumpe S, Eisele MR, Elsasser S, Tian G, Sun S, Moroco JA, Cheng TC, Joshi T, Seibel T, Van Dalen D, Feng XH, Lu Y, Ovaa H, Engen JR, Lee BH, Rudack T, Sakata E, Finley D Nat Commun. 2022 Feb 11;13(1):838. doi: 10.1038/s41467-022-28186-y. PMID:35149681 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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