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PDBsum entry 4cr2
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Contents |
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205 a.a.
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223 a.a.
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204 a.a.
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198 a.a.
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212 a.a.
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222 a.a.
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233 a.a.
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243 a.a.
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250 a.a.
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245 a.a.
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242 a.a.
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243 a.a.
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233 a.a.
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245 a.a.
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359 a.a.
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362 a.a.
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373 a.a.
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381 a.a.
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361 a.a.
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367 a.a.
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849 a.a.
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387 a.a.
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415 a.a.
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431 a.a.
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400 a.a.
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353 a.a.
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272 a.a.
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255 a.a.
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247 a.a.
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197 a.a.
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127 a.a.
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19 a.a.
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813 a.a.
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References listed in PDB file
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Key reference
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Title
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Deep classification of a large cryo-Em dataset defines the conformational landscape of the 26s proteasome.
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Authors
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P.Unverdorben,
F.Beck,
P.ŚLedź,
A.Schweitzer,
G.Pfeifer,
J.M.Plitzko,
W.Baumeister,
F.Förster.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
5544-5549.
[DOI no: ]
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PubMed id
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Abstract
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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-γS 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-γS 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-γS 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.
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