TY  - JOUR
A1  - Pluska, Lukas
A1  - Jarosch, Ernst
A1  - Zauber, Henrik
A1  - Kniß, Andreas
A1  - Waltho, Anita
A1  - Bagola, Katrin
A1  - Delbrück, Maximilian von
A1  - Löhr, Frank
A1  - Schulman, Brenda A.
A1  - Selbach, Matthias
A1  - Dötsch, Volker
A1  - Sommer, Thomas
T1  - The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63-branched ubiquitin chains
T2  - The EMBO journal
N2  - The assembly of a specific polymeric ubiquitin chain on a target protein is a key event in the regulation of numerous cellular processes. Yet, the mechanisms that govern the selective synthesis of particular polyubiquitin signals remain enigmatic. The homologous ubiquitin-conjugating (E2) enzymes Ubc1 (budding yeast) and Ube2K (mammals) exclusively generate polyubiquitin linked through lysine 48 (K48). Uniquely among E2 enzymes, Ubc1 and Ube2K harbor a ubiquitin-binding UBA domain with unknown function. We found that this UBA domain preferentially interacts with ubiquitin chains linked through lysine 63 (K63). Based on structural modeling, in vitro ubiquitination experiments, and NMR studies, we propose that the UBA domain aligns Ubc1 with K63-linked polyubiquitin and facilitates the selective assembly of K48/K63-branched ubiquitin conjugates. Genetic and proteomics experiments link the activity of the UBA domain, and hence the formation of this unusual ubiquitin chain topology, to the maintenance of cellular proteostasis.
KW  - cell stress
KW  - K48-linked
KW  - K63-linked
KW  - polyubiquitin
KW  - ubiquitin-conjugating enzymes
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62098
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-620983
SN  - 1460-2075
N1  - This work was funded by the Deutsche Forschungsgemeinschaft (SO 271/9-1, DO 545/17-1). B.A.S. was supported by the Max Planck Gesellschaft.
VL  - 40
IS  - 6, art. e106094
SP  - 1
EP  - 19
PB  - Wiley
CY  - Hoboken, NJ [u.a.]
ER  -