4jpo | pdb_00004jpo
5A resolution structure of Proteasome Assembly Chaperone Hsm3 in complex with a C-terminal fragment of Rpt1
Structural highlights
FunctionHSM3_YEAST Involved in DNA mismatch repair in slow-growing cells. Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the 19S regulatory complex (RC).[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric alpha-ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt carboxy-terminal tails inserting into pockets of the alpha-ring. Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit. Here we report that the base subassembly of the Saccharomyces cerevisiae proteasome, which includes the Rpt ring, forms a high-affinity complex with the CP. This complex is subject to active dissociation by the chaperones Hsm3, Nas6 and Rpn14. Chaperone-mediated dissociation was abrogated by a non-hydrolysable ATP analogue, indicating that chaperone action is coupled to nucleotide hydrolysis by the Rpt ring. Unexpectedly, synthetic Rpt tail peptides bound alpha-pockets with poor specificity, except for Rpt6, which uniquely bound the alpha2/alpha3-pocket. Although the Rpt6 tail is not visualized within an alpha-pocket in mature proteasomes, it inserts into the alpha2/alpha3-pocket in the base-CP complex and is important for complex formation. Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme. Reconfiguration of the proteasome during chaperone-mediated assembly.,Park S, Li X, Kim HM, Singh CR, Tian G, Hoyt MA, Lovell S, Battaile KP, Zolkiewski M, Coffino P, Roelofs J, Cheng Y, Finley D Nature. 2013 May 23;497(7450):512-6. doi: 10.1038/nature12123. Epub 2013 May 5. PMID:23644457[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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