The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63-branched ubiquitin chains

  • 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.
Author:Lukas Pluska, Ernst Jarosch, Henrik Zauber, Andreas Kniß, Anita Waltho, Katrin BagolaORCiDGND, Maximilian von Delbrück, Frank LöhrORCiD, Brenda A. SchulmanORCiDGND, Matthias Selbach, Volker DötschORCiDGND, Thomas Sommer
Parent Title (English):The EMBO journal
Place of publication:Hoboken, NJ [u.a.]
Document Type:Article
Date of Publication (online):2021/03/15
Date of first Publication:2021/03/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/08/25
Tag:K48-linked; K63-linked; cell stress; polyubiquitin; ubiquitin-conjugating enzymes
Issue:6, art. e106094
Page Number:19
First Page:1
Last Page:19
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.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0