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PDBsum entry 5cw3
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Metal binding protein
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PDB id
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5cw3
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References listed in PDB file
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Key reference
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Title
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Higher-Order assembly of brcc36-Kiaa0157 is required for dub activity and biological function.
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Authors
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E.Zeqiraj,
L.Tian,
C.A.Piggott,
M.C.Pillon,
N.M.Duffy,
D.F.Ceccarelli,
A.F.Keszei,
K.Lorenzen,
I.Kurinov,
S.Orlicky,
G.D.Gish,
A.J.Heck,
A.Guarné,
R.A.Greenberg,
F.Sicheri.
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Ref.
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Mol Cell, 2015,
59,
970-983.
[DOI no: ]
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PubMed id
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Abstract
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BRCC36 is a Zn(2+)-dependent deubiquitinating enzyme (DUB) that hydrolyzes
lysine-63-linked ubiquitin chains as part of distinct macromolecular complexes
that participate in either interferon signaling or DNA-damage recognition. The
MPN(+) domain protein BRCC36 associates with pseudo DUB MPN(-) proteins KIAA0157
or Abraxas, which are essential for BRCC36 enzymatic activity. To understand the
basis for BRCC36 regulation, we have solved the structure of an active
BRCC36-KIAA0157 heterodimer and an inactive BRCC36 homodimer. Structural and
functional characterizations show how BRCC36 is switched to an active
conformation by contacts with KIAA0157. Higher-order association of BRCC36 and
KIAA0157 into a dimer of heterodimers (super dimers) was required for DUB
activity and interaction with targeting proteins SHMT2 and RAP80. These data
provide an explanation of how an inactive pseudo DUB allosterically activates a
cognate DUB partner and implicates super dimerization as a new regulatory
mechanism underlying BRCC36 DUB activity, subcellular localization, and
biological function.
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