Structural highlights
5u4p is a 3 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Gene: | RPN8, YOR261C, O5360 (Baker's yeast), RPN11, MPR1, YFR004W (Baker's yeast), RPS31, RPS37, UBI3, YLR167W, L9470.14 (Baker's yeast) |
| Activity: | Ubiquitinyl hydrolase 1, with EC number 3.4.19.12 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[RPN8_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.[1] [RS27A_YEAST] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, and DNA-damage responses. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). 40S ribosomal protein S31 is a component of the 40S subunit of the ribosome (By similarity). [RPN11_YEAST] Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.[2]
Publication Abstract from PubMed
Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to prevent premature ubiquitin chain removal and substrate escape. Here we reveal the ubiquitin-bound structure of Rpn11 from S. cerevisiae and the mechanisms for mechanochemical coupling of substrate degradation and deubiquitination. Ubiquitin binding induces a conformational switch of Rpn11's Insert-1 loop from an inactive closed state to an active beta hairpin. This switch is rate-limiting for deubiquitination and strongly accelerated by mechanical substrate translocation into the AAA+ motor. Deubiquitination by Rpn11 and ubiquitin unfolding by the ATPases are in direct competition. The AAA+ motor-driven acceleration of Rpn11 is therefore important to ensure that poly-ubiquitin chains are removed only from committed substrates and fast enough to prevent their co-degradation.
An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome.,Worden EJ, Dong KC, Martin A Mol Cell. 2017 Aug 16. pii: S1097-2765(17)30547-6. doi:, 10.1016/j.molcel.2017.07.023. PMID:28844860[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Glickman MH, Rubin DM, Fried VA, Finley D. The regulatory particle of the Saccharomyces cerevisiae proteasome. Mol Cell Biol. 1998 Jun;18(6):3149-62. PMID:9584156
- ↑ Chen L, Romero L, Chuang SM, Tournier V, Joshi KK, Lee JA, Kovvali G, Madura K. Sts1 plays a key role in targeting proteasomes to the nucleus. J Biol Chem. 2011 Jan 28;286(4):3104-18. doi: 10.1074/jbc.M110.135863. Epub 2010 , Nov 12. PMID:21075847 doi:10.1074/jbc.M110.135863
- ↑ Worden EJ, Dong KC, Martin A. An AAA Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome. Mol Cell. 2017 Aug 16. pii: S1097-2765(17)30547-6. doi:, 10.1016/j.molcel.2017.07.023. PMID:28844860 doi:http://dx.doi.org/10.1016/j.molcel.2017.07.023
