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PDBsum entry 5a5b
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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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368 a.a.
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76 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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Structural characterization of the interaction of ubp6 with the 26s proteasome.
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Authors
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A.Aufderheide,
F.Beck,
F.Stengel,
M.Hartwig,
A.Schweitzer,
G.Pfeifer,
A.L.Goldberg,
E.Sakata,
W.Baumeister,
F.Förster.
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Ref.
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Proc Natl Acad Sci U S A, 2015,
112,
8626-8631.
[DOI no: ]
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PubMed id
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Abstract
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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.
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