7qo6: Difference between revisions

Latest revision as of 06:33, 1 October 2025

26S proteasome Rpt1-RK -Ubp6-UbVS complex in the s2 state

Structural highlights

7qo6 is a 11 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 6.3Å
Ligands:	ADP, ATP, GLZ, MG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SEM1_YEAST Versatile protein that might stabilize multiple protein complexes involved in diverse pathways. Subunit of the 26S proteasome which plays a role in ubiquitin-dependent proteolysis. Associates also with the TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Faza MB, Kemmler S, Jimeno S, Gonzalez-Aguilera C, Aguilera A, Hurt E, Panse VG. Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery. J Cell Biol. 2009 Mar 23;184(6):833-46. doi: 10.1083/jcb.200810059. Epub 2009 Mar, 16. PMID:19289793 doi:https://dx.doi.org/10.1083/jcb.200810059
↑ Sone T, Saeki Y, Toh-e A, Yokosawa H. Sem1p is a novel subunit of the 26 S proteasome from Saccharomyces cerevisiae. J Biol Chem. 2004 Jul 2;279(27):28807-16. Epub 2004 Apr 26. PMID:15117943 doi:https://dx.doi.org/10.1074/jbc.M403165200
↑ 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. Allosteric control of Ubp6 and the proteasome via a bidirectional switch. Nat Commun. 2022 Feb 11;13(1):838. doi: 10.1038/s41467-022-28186-y. PMID:35149681 doi:https://dx.doi.org/10.1038/s41467-022-28186-y

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Faza MB, Kemmler S, Jimeno S, Gonzalez-Aguilera C, Aguilera A, Hurt E, Panse VG. Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery. J Cell Biol. 2009 Mar 23;184(6):833-46. doi: 10.1083/jcb.200810059. Epub 2009 Mar, 16. PMID:19289793 doi:https://dx.doi.org/10.1083/jcb.200810059

[2] Sone T, Saeki Y, Toh-e A, Yokosawa H. Sem1p is a novel subunit of the 26 S proteasome from Saccharomyces cerevisiae. J Biol Chem. 2004 Jul 2;279(27):28807-16. Epub 2004 Apr 26. PMID:15117943 doi:https://dx.doi.org/10.1074/jbc.M403165200

[3] 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. Allosteric control of Ubp6 and the proteasome via a bidirectional switch. Nat Commun. 2022 Feb 11;13(1):838. doi: 10.1038/s41467-022-28186-y. PMID:35149681 doi:https://dx.doi.org/10.1038/s41467-022-28186-y

[1]

[2]

[3]

@@ Line 3: / Line 3: @@
 <StructureSection load='7qo6' size='340' side='right'caption='[[7qo6]], [[Resolution|resolution]] 6.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7qo6]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QO6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7qo6]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QO6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qo6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qo6 OCA], [https://pdbe.org/7qo6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qo6 RCSB], [https://www.ebi.ac.uk/pdbsum/7qo6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qo6 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/A0A6A5PYC9_YEASX A0A6A5PYC9_YEASX]] 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.[ARBA:ARBA00003542]
+[https://www.uniprot.org/uniprot/SEM1_YEAST SEM1_YEAST] Versatile protein that might stabilize multiple protein complexes involved in diverse pathways. Subunit of the 26S proteasome which plays a role in ubiquitin-dependent proteolysis. Associates also with the TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation.<ref>PMID:19289793</ref> <ref>PMID:15117943</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7qo6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Proteasome 3D structures|Proteasome 3D structures]]
 == References ==
 <references/>

7qo6: Difference between revisions

Latest revision as of 06:33, 1 October 2025

26S proteasome Rpt1-RK -Ubp6-UbVS complex in the s2 state

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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