5a5b: Difference between revisions
New page: '''Unreleased structure''' The entry 5a5b is ON HOLD until sometime in the future Authors: Aufderheide, A., Beck, F., Stengel, F., Hartwig, M., Schweitzer, A., Pfeifer, G., Goldberg, A.... |
No edit summary |
||
| (8 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Structure of the 26S proteasome-Ubp6 complex== | ||
<SX load='5a5b' size='340' side='right' viewer='molstar' caption='[[5a5b]], [[Resolution|resolution]] 9.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5a5b]] is a 10 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=5A5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A5B FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLZ:AMINO-ACETALDEHYDE'>GLZ</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=5a5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a5b OCA], [https://pdbe.org/5a5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a5b RCSB], [https://www.ebi.ac.uk/pdbsum/5a5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a5b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PSA3_YEAST PSA3_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. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In eukaryotic cells, the 26S proteasome is responsible for the regulated degradation of intracellular proteins. Several cofactors interact transiently with this large macromolecular machine and modulate its function. The deubiquitylating enzyme ubiquitin C-terminal hydrolase 6 [Ubp6; ubiquitin-specific protease (USP) 14 in mammals] is the most abundant proteasome-interacting protein and has multiple roles in regulating proteasome function. Here, we investigate the structural basis of the interaction between Ubp6 and the 26S proteasome in the presence and absence of the inhibitor ubiquitin aldehyde. To this end we have used single-particle electron cryomicroscopy in combination with cross-linking and mass spectrometry. Ubp6 binds to the regulatory particle non-ATPase (Rpn) 1 via its N-terminal ubiquitin-like domain, whereas its catalytic USP domain is positioned variably. Addition of ubiquitin aldehyde stabilizes the binding of the USP domain in a position where it bridges the proteasome subunits Rpn1 and the regulatory particle triple-A ATPase (Rpt) 1. The USP domain binds to Rpt1 in the immediate vicinity of the Ubp6 active site, which may effect its activation. The catalytic triad is positioned in proximity to the mouth of the ATPase module and to the deubiquitylating enzyme Rpn11, strongly implying their functional linkage. On the proteasome side, binding of Ubp6 favors conformational switching of the 26S proteasome into an intermediate-energy conformational state, in particular upon the addition of ubiquitin aldehyde. This modulation of the conformational space of the 26S proteasome by Ubp6 explains the effects of Ubp6 on the kinetics of proteasomal degradation. | |||
Structural characterization of the interaction of Ubp6 with the 26S proteasome.,Aufderheide A, Beck F, Stengel F, Hartwig M, Schweitzer A, Pfeifer G, Goldberg AL, Sakata E, Baumeister W, Forster F Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8626-31. doi:, 10.1073/pnas.1510449112. Epub 2015 Jun 30. PMID:26130806<ref>PMID:26130806</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5a5b" style="background-color:#fffaf0;"></div> | ||
[[Category: Baumeister | |||
[[Category: | ==See Also== | ||
[[Category: Foerster | *[[Proteasome 3D structures|Proteasome 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </SX> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: Aufderheide A]] | |||
[[Category: Baumeister W]] | |||
[[Category: Beck F]] | |||
[[Category: Foerster F]] | |||
[[Category: Goldberg AL]] | |||
[[Category: Hartwig M]] | |||
[[Category: Pfeifer G]] | |||
[[Category: Sakata E]] | |||
[[Category: Schweitzer A]] | |||
[[Category: Stengel F]] | |||