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PDBsum entry 4ldt
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Hydrolase regulator
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PDB id
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4ldt
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Contents |
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255 a.a.
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76 a.a.
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148 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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E2 ubiquitin-Conjugating enzymes regulate the deubiquitinating activity of otub1.
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Authors
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R.Wiener,
A.T.Dibello,
P.M.Lombardi,
C.M.Guzzo,
X.Zhang,
M.J.Matunis,
C.Wolberger.
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Ref.
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Nat Struct Biol, 2013,
20,
1033-1039.
[DOI no: ]
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PubMed id
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Abstract
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OTUB1 is a Lys48-specific deubiquitinating enzyme that forms a complex in vivo
with E2 ubiquitin (Ub)-conjugating enzymes including UBC13 and UBCH5. OTUB1
binds E2~Ub thioester intermediates and prevents ubiquitin transfer, thereby
noncatalytically inhibiting accumulation of polyubiquitin. We report here that a
second role of OTUB1-E2 interactions is to stimulate OTUB1 cleavage of Lys48
polyubiquitin. This stimulation is regulated by the ratio of charged to
uncharged E2 and by the concentration of Lys48-linked polyubiquitin and free
ubiquitin. Structural and biochemical studies of human and worm OTUB1 and UBCH5B
show that the E2 enzyme stimulates binding of the Lys48 polyubiquitin substrate
by stabilizing folding of the OTUB1 N-terminal ubiquitin-binding helix. Our
results suggest that OTUB1-E2 complexes in the cell are poised to regulate
polyubiquitin chain elongation or degradation in response to changing levels of
E2 charging and available free ubiquitin.
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