4ocm: Difference between revisions
New page: '''Unreleased structure''' The entry 4ocm is ON HOLD Authors: Pathare, G.R., Bracher, A. Description: Crystal Structure of the Rpn8-Rpn11 MPN domain heterodimer, crystal form Ib |
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The | ==Crystal Structure of the Rpn8-Rpn11 MPN domain heterodimer, crystal form Ib== | ||
<StructureSection load='4ocm' size='340' side='right'caption='[[4ocm]], [[Resolution|resolution]] 1.99Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4ocm]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OCM FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.99Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4ocm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ocm OCA], [https://pdbe.org/4ocm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ocm RCSB], [https://www.ebi.ac.uk/pdbsum/4ocm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ocm ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RPN8_YEAST RPN8_YEAST] Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.<ref>PMID:9584156</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ATP-dependent degradation of polyubiquitylated proteins by the 26S proteasome is essential for the maintenance of proteome stability and the regulation of a plethora of cellular processes. Degradation of substrates is preceded by the removal of polyubiquitin moieties through the isopeptidase activity of the subunit Rpn11. Here we describe three crystal structures of the heterodimer of the Mpr1-Pad1-N-terminal domains of Rpn8 and Rpn11, crystallized as a fusion protein in complex with a nanobody. This fusion protein exhibits modest deubiquitylation activity toward a model substrate. Full activation requires incorporation of Rpn11 into the 26S proteasome and is dependent on ATP hydrolysis, suggesting that substrate processing and polyubiquitin removal are coupled. Based on our structures, we propose that premature activation is prevented by the combined effects of low intrinsic ubiquitin affinity, an insertion segment acting as a physical barrier across the substrate access channel, and a conformationally unstable catalytic loop in Rpn11. The docking of the structure into the proteasome EM density revealed contacts of Rpn11 with ATPase subunits, which likely stabilize the active conformation and boost the affinity for the proximal ubiquitin moiety. The narrow space around the Rpn11 active site at the entrance to the ATPase ring pore is likely to prevent erroneous deubiquitylation of folded proteins. | |||
Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11.,Pathare GR, Nagy I, Sledz P, Anderson DJ, Zhou HJ, Pardon E, Steyaert J, Forster F, Bracher A, Baumeister W Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):2984-9. doi:, 10.1073/pnas.1400546111. Epub 2014 Feb 10. PMID:24516147<ref>PMID:24516147</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4ocm" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Proteasome 3D structures|Proteasome 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lama glama]] | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Bracher A]] | |||
[[Category: Pathare GR]] | |||
Latest revision as of 20:09, 20 September 2023
Crystal Structure of the Rpn8-Rpn11 MPN domain heterodimer, crystal form IbCrystal Structure of the Rpn8-Rpn11 MPN domain heterodimer, crystal form Ib
Structural highlights
FunctionRPN8_YEAST Acts as a regulatory subunit of the 26S proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.[1] Publication Abstract from PubMedThe ATP-dependent degradation of polyubiquitylated proteins by the 26S proteasome is essential for the maintenance of proteome stability and the regulation of a plethora of cellular processes. Degradation of substrates is preceded by the removal of polyubiquitin moieties through the isopeptidase activity of the subunit Rpn11. Here we describe three crystal structures of the heterodimer of the Mpr1-Pad1-N-terminal domains of Rpn8 and Rpn11, crystallized as a fusion protein in complex with a nanobody. This fusion protein exhibits modest deubiquitylation activity toward a model substrate. Full activation requires incorporation of Rpn11 into the 26S proteasome and is dependent on ATP hydrolysis, suggesting that substrate processing and polyubiquitin removal are coupled. Based on our structures, we propose that premature activation is prevented by the combined effects of low intrinsic ubiquitin affinity, an insertion segment acting as a physical barrier across the substrate access channel, and a conformationally unstable catalytic loop in Rpn11. The docking of the structure into the proteasome EM density revealed contacts of Rpn11 with ATPase subunits, which likely stabilize the active conformation and boost the affinity for the proximal ubiquitin moiety. The narrow space around the Rpn11 active site at the entrance to the ATPase ring pore is likely to prevent erroneous deubiquitylation of folded proteins. Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11.,Pathare GR, Nagy I, Sledz P, Anderson DJ, Zhou HJ, Pardon E, Steyaert J, Forster F, Bracher A, Baumeister W Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):2984-9. doi:, 10.1073/pnas.1400546111. Epub 2014 Feb 10. PMID:24516147[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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