View source for 4cr2


==Deep classification of a large cryo-EM dataset defines the conformational landscape of the 26S proteasome==
<SX load='4cr2' size='340' side='right' viewer='molstar' caption='[[4cr2]], [[Resolution|resolution]] 7.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4cr2]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4b4t 4b4t]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CR2 FirstGlance]. <br>
</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=4cr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cr2 OCA], [https://pdbe.org/4cr2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4cr2 RCSB], [https://www.ebi.ac.uk/pdbsum/4cr2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4cr2 ProSAT]</span></td></tr>
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== Function ==
[[https://www.uniprot.org/uniprot/PSB1_YEAST PSB1_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. PRE3 and PRE4 are necessary for the peptidyl-glutamyl-peptide-hydrolyzing activity.  This subunit is necessary for the peptidylglutamyl-peptide hydrolyzing activity.
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== Publication Abstract from PubMed ==
The 26S proteasome is a 2.5 MDa molecular machine that executes the degradation of substrates of the ubiquitin-proteasome pathway. The molecular architecture of the 26S proteasome was recently established by cryo-EM approaches. For a detailed understanding of the sequence of events from the initial binding of polyubiquitylated substrates to the translocation into the proteolytic core complex, it is necessary to move beyond static structures and characterize the conformational landscape of the 26S proteasome. To this end we have subjected a large cryo-EM dataset acquired in the presence of ATP and ATP-gammaS to a deep classification procedure, which deconvolutes coexisting conformational states. Highly variable regions, such as the density assigned to the largest subunit, Rpn1, are now well resolved and rendered interpretable. Our analysis reveals the existence of three major conformations: in addition to the previously described ATP-hydrolyzing (ATPh) and ATP-gammaS conformations, an intermediate state has been found. Its AAA-ATPase module adopts essentially the same topology that is observed in the ATPh conformation, whereas the lid is more similar to the ATP-gammaS bound state. Based on the conformational ensemble of the 26S proteasome in solution, we propose a mechanistic model for substrate recognition, commitment, deubiquitylation, and translocation into the core particle.

Deep classification of a large cryo-EM dataset defines the conformational landscape of the 26S proteasome.,Unverdorben P, Beck F, Sledz P, Schweitzer A, Pfeifer G, Plitzko JM, Baumeister W, Forster F Proc Natl Acad Sci U S A. 2014 Mar 24. PMID:24706844<ref>PMID:24706844</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4cr2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Proteasome 3D structures|Proteasome 3D structures]]
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Baumeister W]]
[[Category: Beck F]]
[[Category: Foerster F]]
[[Category: Pfeifer G]]
[[Category: Plitzko JM]]
[[Category: Schweitzer A]]
[[Category: Sledz P]]
[[Category: Unverdorben P]]