4cr4
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
[[4cr4]] is a 33 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4bgr 4bgr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CR4 OCA]. <br> | [[4cr4]] is a 33 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4bgr 4bgr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CR4 OCA]. <br> | ||
| - | <b>Related:</b> [[4cr2|4cr2]], [[4cr3|4cr3]]<br> | + | <b>[[Related_structure|Related:]]</b> [[4cr2|4cr2]], [[4cr3|4cr3]]<br> |
<b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br> | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br> | ||
| + | <b>Resources:</b> <span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cr4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cr4 RCSB], [http://www.ebi.ac.uk/pdbsum/4cr4 PDBsum]</span><br> | ||
== Publication Abstract from PubMed == | == 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. | 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. | ||
Revision as of 10:12, 30 April 2014
Deep classification of a large cryo-EM dataset defines the conformational landscape of the 26S proteasome
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