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PDBsum entry 4boz
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References listed in PDB file
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Key reference
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Title
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Otu deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis.
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Authors
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T.E.Mevissen,
M.K.Hospenthal,
P.P.Geurink,
P.R.Elliott,
M.Akutsu,
N.Arnaudo,
R.Ekkebus,
Y.Kulathu,
T.Wauer,
F.El oualid,
S.M.Freund,
H.Ovaa,
D.Komander.
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Ref.
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Cell, 2013,
154,
169-184.
[DOI no: ]
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PubMed id
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Abstract
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Sixteen ovarian tumor (OTU) family deubiquitinases (DUBs) exist in humans, and
most members regulate cell-signaling cascades. Several OTU DUBs were reported to
be ubiquitin (Ub) chain linkage specific, but comprehensive analyses are
missing, and the underlying mechanisms of linkage specificity are unclear. Using
Ub chains of all eight linkage types, we reveal that most human OTU enzymes are
linkage specific, preferring one, two, or a defined subset of linkage types,
including unstudied atypical Ub chains. Biochemical analysis and five crystal
structures of OTU DUBs with or without Ub substrates reveal four mechanisms of
linkage specificity. Additional Ub-binding domains, the ubiquitinated sequence
in the substrate, and defined S1' and S2 Ub-binding sites on the OTU domain
enable OTU DUBs to distinguish linkage types. We introduce Ub chain restriction
analysis, in which OTU DUBs are used as restriction enzymes to reveal linkage
type and the relative abundance of Ub chains on substrates.
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