TY  - JOUR
A1  - Mevissen, Tycho E. T.
A1  - Hospenthal, Manuela K.
A1  - Geurink, Paul P.
A1  - Elliott, Paul R.
A1  - Akutsu, Masato
A1  - Arnaudo, Nadia
A1  - Ekkebus, Reggy
A1  - Kulathu, Yogesh
A1  - Wauer, Tobias
A1  - El Oualid, Farid
A1  - Freund, Stefan M. V.
A1  - Ovaa, Huib
A1  - Komander, David
T1  - OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis
T2  - Cell
N2  - 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/31664
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-316645
SN  - 1097-4172
SN  - 0092-8674
N1  - This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 154
SP  - 169
EP  - 184
PB  - Elsevier
CY  - New York, NY
ER  -